Founder led - This is a big bet on the Exec Chair, Founder – Paul Rennie.

Could we organise a chat with him @Strawman?

Huge market – 72m Osteoarthritis (OA) sufferers in 2020, expect 120m in 2030 (5% Mkt CAGR). 81% are dissatisfied with current treatment. Targeting 10% of the market (not sure how achievable this might be). Dosage to cost US$2.5k per patient p.a. suggesting a US$14bn market opportunity.

Paradigm’s main product is a repurposed drug being trialed to address a huge unmet need - so the potential is huge but range of outcomes are wide.

As it’s repurposed, there is high confidence that the drug is safe (at a given dosage). This removes a huge potential risk at the Phase 3 trial stage.

As it’s unmet need, the "FDA has granted Fast-track designation to the OA program" – they want this to work and are happy to expedite (as long as it does).

Phase 2 trials have been positive in alleviating pain (key end point) and even improving the condition (improving cartalidge thickness).

Check out the Cap Raise Preso for more info - https://www.marketindex.com.au/asx/par/announcements/investor-presentation-30m-capital-raise-3A629518

Disc: Held (small 'research position')

Further to @GazD's updates and enthusiasm on the progress of Paradigm, I've had a look at their recent cap raise and here's my thoughts.

$35m Mkt Cap (@ $0.43 share price), before new shares issued.

Just raised $30m, fully underwritten (Est $28.5m after costs), but spent $22m in R&D in the Sep-23 Quarter alone!!

Now have $69.4m in cash @ Dec-23 to last to mid CY25 / FY25 (without additional licensing revenue).

Massively dilutive as it almost doubles their share count, and will increase shares on issue by > 1.5x if attaching options from Cap Raise are exercised within the year (expiring Dec-24 w Strike @ $0.65).

So, unless I am missing something they will need another funding injection soon I expect.

There are 3 possible sources for this:

1)   Potential partnering deals to provide material additional non-dilutive cash runway. They expect 1 or more in the next 6 months. I would expect the bargaining power to lie with the partner(s).

2)   Options issued in the Cap Raise, if exercised will raise A$33.8m... but only if $SP > $0.65 (51% above raise price of $0.43) by 30-Nov-24. This will require a very positive outlook – most likely based on Phase 2 & 3 trial progress / read outs between now and then.

3)   Another (thesis busting) capital raise...

If there wasn't such a massive potential here this Cap Raise would have been a thesis breaker for me (i.e. mgmt can't allocate capital well enough).

Disc: Held (just started a small 'research position')

And there it is, they’ve addressed the spectre of cashburn, runway and a falling share price. Shame the raise is at such a low price but I guess that’s what happens when you leave the capital situation up in the air and rates go against you/risk off intervenes.

on the upside they claim to now be funded til completion of the phase 3 trial on pentosan in OA which is the potential blockbuster.

although dilution is always a shame and the SP has taken a 30% hit today to be honest I’m actually happier knowing they have runway in front of them as the drug has such potential.

still think this thing is ridiculously undervalued but that’s probably to be expected in current environment

 ASX RELEASE 31 October 2023

FULLY UNDERWRITTEN $30M CAPITAL RAISE TO FUND COMPANY THROUGH TO TOPLINE READ OUT OF PHASE 3 OSTEOARTHRITIS TRIAL IN MID 2025

KEY HIGHLIGHTS

•

• The placement and the institutional offer raised a total of $21.1m and received strong support from new and existing institutional and sophisticated investors in Australia and internationally (Placement).

• The accelerated offer to eligible institutional shareholders has now completed, raising approximately $3.1 million with a take up of 78%.

•

• The pro-forma cash balance at the completion of the Placement and Entitlement Offer will be $69.4 million, with an additional $33.8 million if all options are exercised before they lapse.

• Funds raised under the offer, and the proceeds from the exercise of options, will be used to fund Paradigm through to mid CY25 (without relying on additional licensing revenue, should that be generated), including the expected top-line readout from the Phase 3 OA clinical trial.

• Key upcoming catalysts for the Company include commencement of next stage of Phase 3 OA program, TGA provisional approval, readout of top-line data for phase 2 program for MPS and potential regional licensing agreements for OA and MPS.

 Paradigm announces fully underwritten $30m capital raise comprising an

 $18m placement and a $12m accelerated non renounceable entitlement offer

 (ANREO or Entitlement Offer)

 The 1 for 10 retail entitlement offer of $9m is fully underwritten and is expected

 to open at 9:00am Monday 6 November.

  Paradigm Biopharmaceuticals Ltd (ASX:PAR) (“Paradigm” or “the Company”), a late-stage drug development company focused on delivering new therapies to address unmet medical needs, is pleased to announce that the $30m capital raise announced 30 October 2023 is fully underwritten by lead manager Bell Potter Securities (Bell Potter or the Underwriter).

The Company has completed the $18m placement that has been strongly supported by new and existing institutional and sophisticated Paradigm shareholders. The Company has now received confirmation that the accelerated entitlement offer to eligible institutional shareholders has received take up by existing institutions totalling $3.1m million with a take up rate of 78% from eligible institutional shareholders.

The record date for the retail entitlement offer is 1 November 2023 (Record Date).

Paradigm Managing Director, Paul Rennie commented: “I would like to thank all the existing shareholders for their continued support of Paradigm and would like to welcome the new institutional investors as we continue to progress iPPS as a potential blockbuster therapy for osteoarthritis. To receive such strong support is a great endorsement of the ongoing strength of our clinical assets and focusses the Company on progressing our phase 3 OA clinical program and commercial licensing discussions to achieve value for all Paradigm shareholders."

Capital Raise Summary

 The fully underwritten capital raise of $30.1 million (before costs) will be comprised of:

• a Placement to institutional investors to subscribe for approximately 42 million shares at an issue price of $0.43 per share to raise approximately $18 million; and

• an accelerated non-renounceable Entitlement Offer of 1 share for every 10 shares held by eligible shareholders on the Record Date at an issue price of $0.43 per share to raise approximately $12.1 million.

• Every 4 shares subscribed for and issued under the Entitlement Offer and Placement will be accompanied by 3 free-attaching options exercisable at $0.65 expiring on 30 November 2024.

Replacement Prospectus

The Company has today lodged a replacement prospectus (Prospectus) with ASIC, updating the original prospectus for the Placement and Entitlement Offer dated 30 October 2023. The key differences between the Prospectus and the original prospectus are to disclose the Company's entry into the Underwriting Agreement pursuant to which the Placement and the Entitlement Offer will be fully underwritten by Bell Potter and to include the offer of up to 10,074,426 options on the same terms as the Options under the Placement and Entitlement Offer (Sub-Underwriter Options) to the Underwriter and/or sub-underwriters of the Entitlement Offer and Placement as previously disclosed in the original prospectus.

The material terms of the Underwriting Agreement, including the fees to be paid to Bell Potter in consideration for its underwriting services are also set out in the Prospectus.

Commencement of the Retail Entitlement Offer

The Entitlement Offer is being conducted through:

• an accelerated offer to eligible institutional shareholders in Australia, New Zealand, Hong Kong, Cayman Islands, Singapore, the United Kingdom and the United States (Institutional Offer) which is now completed; and

• an offer to eligible retail shareholders, being retail shareholders with a registered address in Australia or New Zealand (or that the Company has otherwise determined is eligible to participate without any requirement for a prospectus or any other disclosure document to be lodged or registered and who is not in the United States and not acting for the account or benefit of a person in the United States) (Eligible Retail Shareholders) (Retail Offer).

Eligible Retail Shareholders with a registered address in Australia or New Zealand as at 7:00pm (Sydney time) on the Record Date are invited to participate in the Entitlement offer at the same offer price as the Institutional Offer. The Retail Offer will open at 9:00am (Sydney time) Monday 6 November and close at 5:00pm (Sydney time) on Monday 20 November.

Eligible Retail Shareholders will receive a copy of the Prospectus, including a personalised entitlement and acceptance form, which will provide further details of how to participate in the Retail Offer.

The shortfall, if any, will then be placed in accordance with the terms of the Underwriting Agreement. New Shares issued under the Entitlement Offer shortfall will be subscribed for by the Underwriter or sub-underwriter/s, in accordance with the underwriting agreement between the Company and the Underwriter. The Entitlement Offer is fully sub- underwritten by domestic and international institutional investors.

All new shares to be issued under the Entitlement Offer will rank equally with existing PAR fully paid ordinary shares in all respects. New shares and options under the Retail Offer are expected to be issued on Monday 27 November, and commence normal trading on Tuesday 28 November 2023.

Summary of Use of Funds

Paradigm expects to confirm the 2mg/kg twice weekly optimal dose in Q1 CY 2024 and commence enrolment into the next stage of the phase 3 OA program shortly thereafter.

Paradigm is focussed on partnering its clinical assets and expects any licensing transaction to add further funding sources to bring iPPS through to commercialisation in multiple jurisdictions simultaneously.

The proceeds from the offer will be used to fund the Company’s phase 3 OA clinical program and to pay for the costs of the Placement and Entitlement Offer. The proceeds are expected to fund the Company’s OA phase 3 clinical program to the end of CY2024 with the exercise of options expected to provide further runway to mid CY 2025 and past Paradigm’s expected top-line read out from the phase 3 clinical trial.

 Upcoming Catalysts Event

MPS VI phase 2 clinical trials – top-line data.

Phase 3 OA program – FDA protocol review next stage of Phase 3 program.

TGA Provisional Approval OA - submission for next stage determination application.

Phase 3 OA program – next stage enrollment commencement, subject to regulatory agreement.

Regional licensing agreement(s) in OA and MPS.

Target Date

Q4 CY 2023 Q1 CY 2024

Q1 CY 2024 H1 CY 2024 H1 CY 2024

 TGA Provisional Approval OA - dossier submission, pending determination of application approval.

The MPS I and PARA_OA_008 – Peer Review Publications.

Potential expedited or provisional approval submissions for MPS program (Brazil, Australia).

Entitlement Offer and Placement Timetable

Q3 CY 2024 CY 2024 CY 2024

    An indicative timetable for the Entitlement Offer and Placement is set out below (subject to change):

 Event

Lodgement of original prospectus

Announcement of results of the Placement and the Institutional Offer

Lodgement of replacement prospectus Trading halt lifted

Record Date for the Retail Offer

Prospectus despatched to Eligible Retail Shareholders

Addendum to Notice of AGM despatched to Shareholders

Allotment of Shares under the Placement and the Institutional Offer

Quotation of Shares issued under the Placement and the Institutional Offer

Last day to extend the closing date of the Retail Offer

Closing date of the Retail Offer Announcement of results of Retail Offer

Date

Monday, 30 October 2023 Tuesday, 31 October 2023

Tuesday, 31 October 2023

Wednesday, 1 November 2023

7.00pm (AEDT) Wednesday, 1 November 2023

Monday, 6 November 2023

Monday, 6 November 2023

Wednesday, 8 November 2023 (before noon AEDT)

Thursday, 9 November 2023

Wednesday, 15 November 2023 (before noon AEDT)

Monday, 20 November 2023

Thursday, 23 November 2023 (before noon AEDT)

             Allotment of Shares under the Retail Offer and Options under the Entitlement Offer

  Monday, 27 November 2023 (before noon AEDT)

 Quotation of Shares issued under the Retail Offer and Options under the Entitlement Offer

  Tuesday, 28 November 2023

 Paradigm AGM approval to be sought to issue the Placement Options and (if applicable) Sub-Underwriter Options

  Wednesday, 29 November 2023

 Issue of Placement Options and (if Wednesday, 29 November 2023

applicable) Sub-Underwriter Options

(before noon AEDT)

 Quotation of Placement Options and (if Thursday, 30 November 2023 applicable) Sub-Underwriter Options

* The above timetable is indicative only and is subject to change.

-Ends-

  About Paradigm Biopharmaceuticals Ltd.

 Paradigm Biopharmaceuticals Ltd. (ASX:PAR) is a late-stage drug development company driven by a purpose to improve patients’ health and quality of life by discovering, developing, and delivering pharmaceutical therapies. Paradigm’s current focus is developing injectable (subcutaneous) pentosan polysulfate sodium (iPPS) for the treatment of diseases where inflammation plays a major pathogenic role, indicating a need for the anti-inflammatory and tissue regenerative properties of iPPS, such as in osteoarthritis (phase 3) and mucopolysaccharidosis (phase 2).

 Forward Looking Statements

 This Company announcement contains forward-looking statements, including statements regarding anticipated commencement dates or completions dates of preclinical or clinical trials, regulatory developments and regulatory approval. These forward-looking statements are not guarantees or predictions of future performance, and involve known and unknown risks, uncertainties and other factors, many of which are beyond our control, and which may cause actual results to differ materially from those expressed in the statements contained in this presentation. Readers are cautioned not to put undue reliance on forward-looking statements.

To learn more please visit: https://paradigmbiopharma.com Approved for release by the Paradigm Board of Directors.

FOR FURTHER INFORMATION PLEASE CONTACT: Simon White

Director of Investor Relations

Tel: +61 404 216 467

Paradigm Biopharmaceuticals Ltd

ABN: 94 169 346 963

Level 15, 500 Collins St, Melbourne, VIC, 3000, AUSTRALIA Email: investorrelations@paradigmbiopharma.com

@ slomo

i read your valuation with interest My previous valuation was absurdly high and no doubt I have sunk cost in this stock which clouds my view.

im wondering now whether the greatest risk aside from an unexpected dud result is just that it gets bought out for 2-300% of the current SP. would be absolute chicken feed to big pharma and they would get potentially a blockbuster drug… I would be gutted having ridden this thing for more than 5 years

Paradigm's quarterly cash activities report below:

In summary: made good progress on research/evidence base but spent a truckload of money. So much so that the market has shat itself and dumped the stock 20%. Commentary suggests ongoing costs will fall significantly but realistically it seems likely there will be another cap raise prior to commercialisation which I suppose is what the market is selling off.

For me it's more of the same do nothing. I can see the results (even interim results) are likely to be out in the next 12 month period and could be a real catalyst for improved SP which would make raising more funds less of an issue. On the downside if the SP languishes and they have to raise at an even lower SP it's pretty awful dilution even if the drug works incredibly well.

Paradigm Biopharmaceuticals Ltd. (ASX:PAR) (“Paradigm” or “the

Company”) is pleased to provide its quarterly update for the three months ended

31 December 2023 to accompany its Appendix 4C cash flow report for the period.

• Cash balance as of 31 December 2023 was $33.5m (on 30 September 2023 it was

$33.6m).

• During the period Paradigm announced a $30.1 million capital raise (before costs)

comprising a fully underwritten $18m placement and $12m accelerated non

renounceable entitlement offer.

• Paradigm has lodged its R&D Tax Incentive refund claim for FY23 and is awaiting

receipt of the $7.2m refund, expected during Q1 CY24.

• Research and development expenditure for the quarter was $27.06m compared to

the previous quarter of $21.9m. This spend in Q2 FY24 was largely related to costs

incurred during the prior quarter on the Stage 1 dose finding activities of Phase 3

clinical trial, including recruitment, screening, dosing and follow-up of the final

patients enrolled in the study. The cost also includes activities related to the close-

out of stage 1 of the PARA_OA_ 002 phase 3 clinical program. Close-out

procedures for clinical trials require all sites to be monitored by Paradigm’s clinical

research organization and Paradigm staff, to comply with the clinical trial

regulations.

• The costs of the interim analysis performed on initial 300 participants on

PARA_OA_002 are also included in the December quarter. Since completing stage

1 of the phase 3 PARA_OA_002 study in late November 2023, the December

spending for new patient activity costs has significantly reduced. It is forecast that

costs going forward will continue to decline, as study closure completes. All ongoing

and future activities will focus on delivering the next phase of the phase 3 OA trial.

• R&D spend during the December quarter also related to clinical and quantitative

MRI data analysis and completion of the PARA_OA_008 phase 2 clinical trial

activities. The spend also included end of study analysis and shut down cost for the

MPS VI phase 2 study, and an ongoing New Drug Application required nonclinical

studies relating to our OA clinical program.

• The quarter also saw payments related to continuing activities described in the

outlook below.

• In accordance with Listing Rule 4.7C.3 and as noted in item 6 of the Appendix 4C

Cashflow Statement, payments to related parties and their associates during the

quarter ended 31 December 2023 were fees of $57K, which includes $52K for

payment of Director fees, and $5K for legal fees to BioMeltzer (a company related

to Paradigm NED, Amos Meltzer).

QUARTERLY ACTIVITIES & OUTLOOK

Paradigm is pleased to provide an update on continuing activities.

Phase 3 Clinical Program

Paradigm reported in October 2023 findings from an interim analysis conducted once the

first 300 participants from the PARA_OA_002 clinical trial reached day 56 of the study.

The doses (less than 2 mg/kg twice weekly) included in the dose determination part of

phase 3 trial did not meet the prespecified performance threshold, which was based on

prior outcome data produced with the 2mg/kg twice weekly dosing regimen. Following

these findings, Paradigm has prepared a new protocol for the next stage of the phase 3

clinical program using the 2mg/kg twice weekly dose regimen of iPPS which has

demonstrated consistent positive data in the PARA_OA_008, PARA_005 (previous phase

2b) studies and the TGA Special Access Scheme.

Stage 1 activities for the PARA_OA_002 phase 3 clinical trial concluded during the quarter

with the study completing the randomisation of 579 subjects demonstrating Paradigm’s

ability to enrol suitable study participants through the many recruitment initiatives

implemented for the global phase 3 study.

Paradigm remains on track for the protocol review by the US FDA to implement the 2mg/kg

twice weekly dosing regimen into the next stage of the OA phase 3 program, anticipated

in Q1 CY2024. Enrolment activities for next stage of the phase 3 OA clinical program are

expected to commence in Q2 CY 2024.

R&D Expenditure

Paradigm’s expenditure over the last three quarters has been unusually high as Paradigm

has invested heavily in the first stage of the phase 3 clinical program. The activities relating

to the spend include:

• Increased clinical trial site activations and initiatives to support subject recruitment,

• PARA_OA_002 Interim Analysis,

• Close out of stage 1 PARA_OA_002 and PARA_OA_006 studies.

Subject Recruitment

Through the second half of CY2023, Paradigm increased its target clinical trial sites from

80 to 120 clinical trial site activations to support the recruitment increased initiatives

undertaken by the Company. The Phase 3 clinical program has activated sites across

seven countries, comprising Australia, the US and Canada in North America, and the UK,

Belgium, Poland, and Czechia in the EU. The additional trial sites activated aided to

Paradigm to meet the reported 100% enrolment target of June 2023 which was reported

at the beginning of July 2023. The significant one-off upfront investment in the trial setup

costs in the stage 1 of the phase 3 trial ensures trial sites are trained and available to

commence with next stage of the phase 3 clinical program, thus streamlining the

recruitment and enrolment process.

As Paradigm reached the increased target for site activation and these clinical trial sites

became familiar with the study design, it enabled an increase in the number of participants

directed to these sites through the utilisation of several recruitment initiatives. The

implemented initiatives include the introduction of 1nHealth, SubjectWell, and Paradigm’s

partnership with NFL Alumni Health, which together increased the volume of potential

participants to study sites for screening and randomisation. Paradigm also launched a

dedicated clinical trial website www.Hope4OA.com, an ethics-approved easy-to-use public-

facing website for providing trial information and access Paradigm’s OA clinical trials. The

implementation of these recruitment initiatives in stage 1 have enabled identification of

potential participants for stage 2 of the phase 3 study.

Paradigm expects the investment in these activities upfront to enhance the efficiency of

the next stage of the phase 3 clinical trial and mitigate any potential delays.

Interim Analysis

An interim analysis was conducted ahead of schedule to determine the performance of the

three iPPS doses in stage 1 of PARA_OA_002 clinical trial against placebo. This was

conducted following reported data from the phase PARA_OA_008 clinical trial

demonstrating the once weekly iPPS dosing regimen was not providing sufficient clinical

results to that of the 2mg/kg twice weekly Paradigm has reported across multiple programs.

Costs associated with the interim analysis included Clinical Research Organisation (CRO)

and Data Monitoring Committee to analyse data on the first 300 participants who had

reached Day 56. The interim analysis provided Paradigm an earlier indication of the optimal

dose and aided the preparation of the clinical protocol for the next stage of the phase 3 OA

program ahead of schedule.

Phase 3 Stage 1 close out activities

Paradigm completed activities associated with the close out of stage 1 of PARA_OA_002

clinical trial and the PARA_OA_006 extension study. Close-out is a process to ensure all

clinical trial related activities are appropriately reconciled, recorded, and reported at the end

of a trial in accordance with the protocol, standard operating procedures (SOPs) good

clinical practice (GCP), and all other applicable regulatory requirements. Close-out is

integral to the quality control of a clinical trial and is designed to ensure quality of the study

according to Sponsor requirements and to ensure that all necessary documents are in place

should it be necessary for the trial information to be retrieved or inspected, by regulatory

agencies, in the future. Paradigm required the close-out to be conducted in accordance with

the said SOPs and with GCP so that the clinical data could be used in discussion with the

US FDA regarding the minimal effective dose discussions and the revised clinical trial

protocol and at the time of Paradigm’s New Drug Application (NDA) submission.

Cost Containment Measures

As discussed during the capital raise, aggressive cost containment measures have been

implemented to ensure capital is being directed toward completion of the phase 3 OA

clinical trial. Paradigm’s financial commitment to the MPS clinical program has now

completed with a reduced headcount in the MPS clinical team implemented following the

completion of the phase 2 studies in MPS I and VI. Paradigm is actively seeking to partner

this clinical asset to progress iPPS for treatment of MPS toward commercialisation.

Ongoing overheads have been reduced throughout this cost containment phase by over

$1m per quarter which will come into effect from January 2024, with further reductions

planned over the coming months.

Forecast cash outflow for the March 2024 quarter is expected to be $8 - $11m (including

R&D refund) and the June 2024 quarter expected to be in the $6m - $8m range which is

inclusive of phase 3 stage 2 restart costs.

Paradigm has issued short term options (Nov 2024 expiry) as a part of the 2023 capital

raise exercisable at $0.65. Exercise of the outstanding options is expected to add an

additional $33m (approximate).

PARA_OA_008 Phase 2 Clinal Trial

Paradigm’s PARA_OA_008 clinical trial concluded during the December quarter with the

significant data from the 12-month clinical data and 6-month quantitative analysis reported.

The PARA_OA_008 clinical trial phase 2 trial data showing efficacy of iPPS on both

objective (MRI analysis) and subjective measures (patient reported outcomes) compared

to placebo, demonstrates that iPPS both treats the symptoms of OA and has the potential

to preserve and/or regenerate joint tissues.

OBJECTIVE DATA MEASURES Reported (Day)

Improvement in synovial fluid biomarkers associated with OA

disease progression.

56 & 168

Improvement in structural changes in the knee determined by MRI. 168

SUBJECTIVE DATA MEASURES Reported

Significant improvement in mean change from baseline in WOMAC

pain, function, and overall scores.

56, 168 & 365

Significant improvement in Patient Global Impression of Change

(PGIC)

365

During the December quarter Paradigm reported durable and significant responses in

WOMAC scores for pain (p=0.054), function (p=0.048), stiffness and overall (p=0.054)

were observed for iPPS twice weekly compared to placebo control through to Day 365.

The outstanding results for iPPS compared to placebo were strengthened through the

reporting that cumulative rescue pain medication use was over five times higher in the

placebo group compared to iPPS group at Day 365.

This data is a significant outcome for Paradigm as no OA drug has previously shown

durable and meaningful improvements in pain and function at 12 months after a single

course of treatment.

The Company also reported in October quantitative MRI analysis results at the day 168

follow-up from the phase 2 PARA_OA_008 clinical trial, demonstrated that a single 6-week

treatment of iPPS treatment at 2mg/kg twice weekly results in an increase in overall

cartilage thickness (p=0.05) and cartilage volume (p=0.07) compared to a decrease in the

placebo group. Bone marrow lesions (-17%) and synovitis (-1%) were also decreased in

the knee joint following iPPS administration to day 168 compared to small increases in the

placebo group.

The above results of the successful phase 2 clinical trial demonstrate that iPPS both treats

the symptoms of OA and preserves and/or regenerates joint tissues. This is significant from

a commercial perspective because the disease modifying effects of iPPS observed in the

PARA_OA_008 phase 2 clinical trial are expected to support a greater reimbursement

compared to that which would be expected for a therapeutic that only treat the symptoms

of OA.

OA remains the most prevalent form of joint disease, affecting up to 16% of the population in

the developed world, with more than 72 million people in the US, EU5, Canada and

Australia suffering from osteoarthritis.1 The prevalence of OA is increasing in line with the

aging population and increasing rates of obesity. By 2030 the number of people suffering

from OA in the US is predicted to increase by 86% to 67 million.2

OA has a significant impact on day-to-day functioning and, although the levels of pain and

disability may fluctuate, it has no known cure or spontaneous remission and is associated

with irreversible structural damage and progression over time. Presently there are no drugs

approved that can prevent, stop, or even restrain progression of OA. Moreover, the

available medications that claim to mitigate the pain of OA have numerous risk/benefit

considerations and market research indicates that only 19% of knee OA patients are

satisfied with currently available treatments. 2,3

There is an urgent unmet need for a new therapy for OA. This successful phase 2 clinical

trial has provided important data for Paradigm to progress with the TGA Provisional

Approval application, which would expedite the pathway to marketing approval of iPPS in

Australia.

Capital Raising

Paradigm announced on the 30th of October, a fully underwritten $30.1 million (before costs

of $1.76m) capital raising, comprising:

• a placement to institutional investors of approximately 42 million Shares at an issue

price of $0.43 per Share raising approximately $18 million;

• an accelerated non-renounceable Entitlement Offer of 1 Share for every 10 Shares

held by eligible shareholders at an issue price of $0.43 per Share raising

approximately $12.1 million; and

• 3 free-attaching Options for every 4 Shares subscribed for and issued under the

Entitlement Offer and Placement.

The proceeds from the capital raise are being utilised for the Company’s phase 3 OA

clinical program.

Paradigm Board Changes

During the December quarter Non-Executive Director, Mr John Gaffney stepped down from

the Paradigm board following 9-years of service. Non-Executive Director, Helen Fisher also

informed the Paradigm Board during the period that she will be stepping down from the

position as Non-Executive Director on the appointment of a replacement Non-Executive

Director, to focus on other commitments going forward. The Paradigm Board commenced

a search for an Independent Non-Executive Director with commercial experience and

financial expertise and an Independent Chair during the December quarter. Paradigm

expects to make an announcement on additions to the board during H1 CY2024.

Mucopolysaccharidosis VI

The MPS VI study has completed however, the MPS VI data analysis encountered an

unforeseen delay with the service provider conducting the GAG analysis for the phase 2

clinical trial. This is a highly specialised analytical technique with only a small number of

service providers available globally. Paradigm expects to release the top-line data next

week.

Global Conferences

American College of Rheumatology (ACR) Convergence 2023: In November Dr Mukesh

Ahuja, Paradigm Global Head of Osteoarthritis, presented a poster at the ACR

Convergence 2023 held November 10–15 at the San Diego Convention Centre in San

Diego, California. The poster detailing data from the PARA_OA_008 clinical trial on the

therapeutic effects of iPPS on clinical and disease modifying outcomes in subjects with

knee osteoarthritis.

Company Outlook

Phase 3 OA Clinical Program

Paradigm met with US FDA on the 10th of January 2024 to discuss outstanding

requirements for the next stage of the Phase 3 clinical program in Osteoarthritis. Paradigm’s

clinical and regulatory teams are preparing the documentation for submission of updated

nonclinical data to the Agency ahead of the submission of the clinical protocol to the FDA.

The program has FDA granted Fast-track designation and the timeline for the review is

expected in Q1 CY2024. Paradigm plans to proceed with the dose of 2mg/kg twice weekly

for registration studies. Enrolment activities for next stage of the phase 3 OA program are

expected to commence in Q2 CY2024.

TGA Provisional Approval Application

Paradigm is progressing with its TGA Provisional marketing approval in Australia for iPPS,

which is expected to expedite the pathway to revenues. The next stage of the TGA

Provisional Approval pathway, the determination application remains on track with the

determination application planned to be submitted to the TGA toward the end of the current

quarter (Q1 CY2024). Should this prove successful, Paradigm will prepare a full dossier for

submission to the final stage of the TGA provisional approval application process.

Business Development

Paradigm continues to progress business development activities with regional partnering

companies with the aim to have at least one regional partnering by the end of June 2024.

Discussions are ongoing with a number of potential partners. Updates will be provided when

appropriate.

Other Activities

• Paradigm’s PARA_OA_008 phase 2 clinical data has been selected for podium

presentations at two global orthopedic and OA conference. Dr Mukesh Ahuja,

Paradigm’s Global Head of Osteoarthritis will present data from the phase 2 clinical

trial evaluating the clinical and disease modifying outcomes of iPPS in knee OA at

the:

o Orthopedic Research Society (ORS) Annual Meeting 2024, 2–6 February:

Paradigm submitted a late-breaking abstract to the ORS selection committee

following the release of the PARA_OA_008 12-month clinical and 6-month

quantitative MRI data. The abstract titled “The therapeutic effects of pentosan

polysulfate sodium on clinical and disease modifying outcomes in moderate

to severe knee osteoarthritis” was selected for a presentation during the late-

breaking podium session; and

o Osteoarthritis Research Society International (OARSI) 2024, 18–21 April:

Paradigm’s recent clinical and disease modifying outcome data from the

PARA_OA_008 phase 2 clinical trial was reviewed by the OARSI panel and

selected for a podium presentation during the conference.

• Paradigm has lodged the FY23 R&D Tax Incentive Scheme refund claim. The

refund of approximately $7.2m was anticipated to be received during Q4 CY2023,

however it is now expected in Q1 CY2024.

• The overall results produced in the PARA_OA_008 phase 2 clinical trial and MPS-I

study are currently being compiled into a manuscript for peer review and publication.

Both are expected to be published during CY2024.

About Paradigm Biopharmaceuticals

Paradigm Biopharmaceuticals Ltd. (ASX:PAR) is a late-stage drug development company

driven by a purpose to improve patients’ health and quality of life by discovering,

developing, and delivering pharmaceutical therapies. Paradigm’s current focus is

developing iPPS for the treatment of diseases where inflammation plays a major

pathogenic role, indicating a need for the anti-inflammatory and tissue regenerative

properties of PPS, such as in osteoarthritis (phase 3) and mucopolysaccharidosis (phase

2).

Forward Looking Statements

This Company announcement contains forward-looking statements, including statements

regarding anticipated commencement dates or completions dates of preclinical or clinical

trials, regulatory developments, and regulatory approval. These forward-looking

statements are not guarantees or predictions of future performance, and involve known

and unknown risks, uncertainties and other factors, many of which are beyond our control,

and which may cause actual results to differ materially from those expressed in the

statements contained in this presentation. Readers are cautioned not to put undue reliance

on forward-looking statements.

References

1 Global Health Data Exchange, Institute for Health and Metrics Evaluation, University of Washington. Accessed June 2021

http://ghdx.healthdata.org/gbd-results-tool.

2 OARSI. Osteoarthritis: A Serious Disease, Submitted to the U.S. Food and Drug Administration December 1, 2016.

3 Matthews GL, Hunter DJ. Emerging drugs for osteoarthritis. Expert Opin Emerg Drugs. 2011;16(3):479-491.

doi:10.1517/14728214.2011.576670.

Authorised for release by the Paradigm Board of Directors.

FOR FURTHER INFORMATION PLEASE CONTACT:

Simon White

Director of Investor Relations

Tel: +61 404 216 467

Paradigm Biopharmaceuticals Ltd.

ABN: 94 169 346 963

Level 15, 500 Collins St, Melbourne, VIC, 3000, AUSTRALIA

Email: investorrelations@paradigmbiopharma.com

Rule 4.7B

ASX Listing Rules Appendix 4C (17/07/20) Page 1

+ See chapter 19 of the ASX Listing Rules for defined terms.

Appendix 4C

Quarterly cash flow report for entities

subject to Listing Rule 4.7B

Name of entity

Paradigm Biopharmaceuticals Limited

ABN Quarter ended (“current quarter”)

94 169 346 963 31 December 2023

Consolidated statement of cash flows Current quarter

$A’000

Year to date (6

months)

$A’000

1. Cash flows from operating activities

- 301.1 Receipts from customers

1.2 Payments for

(27,064) (49,004)(a) research and development

(b) product manufacturing and operating

costs

- -

(c) advertising and marketing (137) (137)

(d) leased assets (26) (37)

(e) staff costs (641) (1,204)

(f) administration and corporate costs (772) (1,300)

1.3 Dividends received (see note 3) - -

1.4 Interest received 86 635

1.5 Interest and other costs of finance paid (3) (6)

1.6 Income taxes paid - -

1.7 Government grants and tax incentives - -

1.8 Other (provide details if material) - -

1.9 Net cash from / (used in) operating

activities

(28,557) (51,023)

2. Cash flows from investing activities

- -

2.1 Payments to acquire or for:

(a) entities

(b) businesses - -

(c) property, plant and equipment - -

(d) investments - -

(e) intellectual property - -

(f) other non-current assets - -Appendix 4C

Quarterly cash flow report for entities subject to Listing Rule 4.7B

ASX Listing Rules Appendix 4C (17/07/20) Page 2

+ See chapter 19 of the ASX Listing Rules for defined terms.

Consolidated statement of cash flows Current quarter

$A’000

Year to date (6

months)

$A’000

2.2 Proceeds from disposal of:

- -(a) entities

(b) businesses - -

(c) property, plant and equipment - -

(d) investments - -

(e) intellectual property - -

(f) other non-current assets - -

2.3 Cash flows from loans to other entities - -

2.4 Dividends received (see note 3) - -

2.5 Other (provide details if material) - -

2.6 Net cash from / (used in) investing

activities

- -

3. Cash flows from financing activities

30,117 30,117

3.1 Proceeds from issues of equity securities

(excluding convertible debt securities)

3.2 Proceeds from issue of convertible debt

securities - -

3.3 Proceeds from exercise of options - -

3.4 Transaction costs related to issues of

equity securities or convertible debt

securities

(1,763)

-

(1,763)

-

3.5 Proceeds from borrowings - -

3.6 Repayment of borrowings (lease liabilities) (8) (51)

3.7 Transaction costs related to loans and

borrowings - -

3.8 Dividends paid - -

3.9 Other (Limited recourse loan repaid under

ESP)

- -

3.10 Net cash from / (used in) financing

activities

28,346 28,303

4. Net increase / (decrease) in cash and

cash equivalents for the period

33,559 56,379

4.1 Cash and cash equivalents at beginning of

period

4.2 Net cash from / (used in) operating

activities (item 1.9 above) (28,557) (51,023)

Paradigm will present at multiple international congresses. Doesn’t hurt to have some peer review and awareness but hardly market sensitive I think.

bring on interim results that might be truly market sensitive!

 ASX RELEASE 30 January 2024

Paradigm’s PARA_OA_008 Clinical Data Selected for Podium Presentations at Major Orthopaedic & OA Conferences

KEY HIGHLIGHTS

• Orthopaedic Research Society (ORS) Annual Meeting 2024, 2–6 February: Abstract accepted for a late-breaking podium presentation during the conference. The abstract details the therapeutic effects of pentosan polysulfate sodium on clinical and disease modifying outcomes in moderate to severe knee osteoarthritis.

• Osteoarthritis Research Society International (OARSI) 2024, 18–21 April: Paradigm’s recent clinical and disease modifying outcome data from the PARA_OA_008 phase 2 clinical trial accepted for podium presentation.

• Acceptance for podium presentations at two leading global medico-scientific conferences in the fields of orthopaedics and osteoarthritis demonstrates the strength and interest of Paradigm’s PARA_OA_008 data amongst our peers.

Paradigm Biopharmaceuticals Ltd (ASX:PAR) (“Paradigm” or “the Company”), a late-stage drug development company focused on delivering new therapies to address unmet medical needs, is pleased to report abstracts of recent data from the successful PARA_OA_008 phase 2 clinical trial have been accepted for oral podium presentations at the 2024 ORS Annual Meeting (California), and the 2024 OARSI World Congress on Osteoarthritis (Vienna, Austria). Conference material presented will be available on the Paradigm website following the conclusion of each conference.

Paradigm Managing Director, Mr Paul Rennie said: “To have our clinical and structural improvement data from the successful PARA_OA_008 phase 2 trial selected for podium presentations at two separate prestigious international scientific conferences, is a testament to the Paradigm clinical program and the impressive effects of iPPS on knee osteoarthritis.

Osteoarthritis impacts an estimated 10 percent of the world’s population over the age of 60 and represents an area of high unmet need for new

therapies which can improve patient outcomes.”

  The phase 2 PARA_OA_008 randomised, double-blind, placebo-controlled, multicentre study evaluating the disease modifying potential of injectable pentosan polysulfate sodium (iPPS) in subjects with knee osteoarthritis (OA) demonstrated not only durable and beneficial effect on pain, function, and the patient’s impression of improvement out to 12 months but also showed improvements in the underlying disease through MRI analysis as early as 6 months following a single 6-week treatment course.

 It provides further validation that the data being produced by iPPS for the

 treatment of knee OA patients is truly world class and is being recognised by a global

 audience of our peers.

 Orthopaedic Research Society 2024 Annual Meeting

Dr Mukesh Ahuja, Paradigm’s Global Head of Osteoarthritis, will be conducting an oral presentation at the ORS 2024 Annual Meeting to be held at the Long Beach Convention Centre in California, USA, from 2–4 February 2024.

Paradigm submitted a late-breaking abstract to the ORS selection committee following the release of the PARA_OA_008 12-month clinical and 6-month quantitative MRI data. The abstract titled “The therapeutic effects of pentosan polysulfate sodium on clinical and disease modifying outcomes in moderate to severe knee osteoarthritis” was selected for a presentation during the late-breaking podium session. Only those abstracts deemed to be of the highest interest and impact to congress attendees are selected for late-breaking presentations.

The ORS Annual Meeting is the largest scientific meeting in the world dedicated solely to the field of research related to the musculoskeletal system and orthopaedics. Meeting attendees include the top basic, translational, and clinical research experts in the world representing academia, industry/private sector, government, and private practice. The meeting provides a platform to share cutting-edge research findings and innovations in the field of musculoskeletal research with a diverse audience of orthopaedic experts.

2024 OARSI World Congress on Osteoarthritis

Dr Mukesh Ahuja, Paradigm’s Global Head of Osteoarthritis, will present data from the phase 2, randomised, double-blinded PARA_OA_008 clinical trial exploring the disease modifying potential of iPPS in subjects with knee OA. The abstract titled “Effects of pentosan polysulfate sodium on clinical outcomes and disease modifying biomarkers in moderate to severe knee osteoarthritis” was reviewed by the OARSI panel and selected for a podium presentation during the conference.

Additionally, Dr Donna Skerrett, Paradigm’s Chief Medical Officer has again

clinical updates from selected companies in clinical development. Dr. Donna Skerrett, Paradigm's Chief Medical Officer has been invited to present the iPPS technology, clinical

translation, and learnings from Paradigm's ongoing OA clinical program.

will facilitate

About Paradigm Biopharmaceuticals

Paradigm Biopharmaceuticals Ltd. (ASX:PAR) is a late-stage drug development company driven by a purpose to improve patients’ health and quality of life by discovering, developing, and delivering pharmaceutical therapies. Paradigm’s current focus is developing injectable (subcutaneous) pentosan polysulfate sodium (iPPS) for the treatment of diseases where inflammation plays a major pathogenic role, indicating a need for the anti-inflammatory and tissue regenerative properties of iPPS, such as in osteoarthritis (phase 3) and mucopolysaccharidosis (phase 2).

  The annual OARSI Congress is the pre-eminent multidisciplinary global forum to showcase and display cutting-edge OA research from academia and industry worldwide.

 The global conference will be held in Vienna, Austria between 18–21 April 2024.

 officially invited to speak at the Clinical Trials Symposium (CTS) scheduled for the day

been

 prior to the commencement of the 2024 OARSI World Congress. The CTS invites

 Furthermore, due to the successful reception last year, Paradigm will also again conduct

 a 15-minute theatre presentation session

which provides

an additional opportunity to

 expand upon Paradigm’s OA clinical development program and

further

 interaction with congress attendees.

 To learn more please visit: www.paradigmbiopharma.com

FOR FURTHER INFORMATION PLEASE CONTACT:

Simon White

Director of Investor Relations

Tel: +61 404 216 467

Paradigm Biopharmaceuticals Ltd ABN: 94 169 346 963

Level 15, 500 Collins St, Melbourne, VIC, 3000, AUSTRALIA Email: investorrelations@paradigmbiopharma.com

This is progress but also highlights the slow progress the business is making. They would have been disappointed to have had to go back and provide this evidence to the FDA but having got it together is obviously good. Unfortunately it's still a way from phase 3 trial results which is the endgame here. I'm confident from the evidence already released that the drug works but the cashburn is unbelievable and they JUST NEED TO GET THEIR PHASE 3 TRIAL DONE! argh. So frustrated.

ASX RELEASE 19 April 2024

PARADIGM CONFIRMS SUBMISSION TO THE US FDA

TO PROGRESS THE PHASE 3 OA PROGRAM

Paradigm Biopharmaceuticals Ltd (ASX:PAR) (“Paradigm” or “the Company”), a

late-stage drug development company focused on delivering new therapies to address

unmet medical needs, is pleased to announce the submission of key documents to the

US Food and Drug Agency (FDA, the Agency) for review and agreement on the

progression of the phase 3 clinical program in osteoarthritis.

Paradigm has submitted to the US FDA a response to the Type D meeting held on 10

January 2024.

Paradigm’s response sets out the results of five nonclinical studies and data from the

successful phase 2 clinical trial, PARA_OA_008, as well as available clinical data from

600 participants dosed in stage 1 of PARA_OA_002. These additional data were collected

following Paradigm’s Investigational New Drug (IND) submission to the Agency in March

2021 (see ASX release), most of which have not previously been submitted nor reviewed

by the FDA. These data provide a detailed justification for the clinical development for

iPPS with the dosing regimen of 2 mg/kg twice weekly for 6 weeks of initial therapy.

Paradigm also submitted a draft of the phase 3 pivotal clinical trial protocol for agency

review and comment.

The response package to the US FDA has been submitted as directed by the Agency,

through a request for review pathway. The request for review pathway does not have

strict Prescription Drug User Fee Act (PDUFA) Agency response timelines, although

feedback is typically received within three months.

The key items addressed in the Type D response submission to the FDA include:

• The minimal effective dose justification.

• Additional nonclinical studies completed to GLP standards to address previously

noted adrenal findings.

• Draft clinical trial protocol.

• Revised safety monitoring and mitigation plan.

Subject to FDA clearance, Paradigm intends to promptly move forward with subject

enrolment into the phase 3 clinical trial (PARA_OA_012) in 2H CY2024. Clinical trial sites

in Australia and the US are planned to commence preparation activities during this quarter

(Q2 CY2024) to move the phase 3 program forward as quickly and efficiently as possible.

Paradigm Managing Director, Mr Paul Rennie commented: “This is important progress

for Paradigm as we deliver a significant amount of new data to the US FDA for review to

progress to the next stage of the phase 3 OA program. Since Paradigm’s IND submission

in March 2021, we have treated close to 700 participants under a clinical trial setting with

various iPPS doses, which provides strong justification that 2 mg/kg twice weekly is the

lowest effective dose with which to move forward. We look forward to receiving the FDA’s

feedback and remain ready to answer any further questions. We look forward to updating

all our investors in the coming months on the outcome of the agency's review and planned

execution of the phase 3 clinical program. I would like to thank our investors for their

ongoing support as we strive to bring the exciting potential of iPPS to market for those

suffering with osteoarthritis.”

Next Steps

Paradigm will now finalise the TGA provisional approval determination application for

submission. The determination application will include information from a manuscript

detailing the outcomes from the PARA_OA_008 phase 2 clinical trial and a manuscript

providing a comparison of iPPS clinical data with other available treatments for

osteoarthritis. Should the determination application decision be positive, Paradigm will

prepare a full dossier submission for TGA provisional approval marketing authorisation.

Provisional approval offers significant benefits to both patients and manufacturers.

Patients gain access to potential life-saving treatments for life-threatening and seriously

debilitating conditions sooner, particularly for those lacking satisfactory alternatives. For

manufacturers, it provides an opportunity to bring innovative therapies to market faster,

while gathering additional data to support full approval. TGA provisional marketing

approval for iPPS in Australia would expedite the pathway to revenues. The completed

manuscripts are being prepared and will be submitted to separate journals for peer-review

and publication.

-Ends-

About Paradigm Biopharmaceuticals Ltd.

Paradigm Biopharmaceuticals Ltd. (ASX:PAR) is a late-stage drug development

company driven by a purpose to improve patients’ health and quality of life by discovering,

developing, and delivering pharmaceutical therapies. Paradigm’s current focus is

developing injectable (subcutaneous) pentosan polysulfate sodium (iPPS) for the

treatment of diseases where inflammation plays a major pathogenic role, indicating a

need for the anti-inflammatory and tissue regenerative properties of iPPS, such as in

osteoarthritis (phase 3) and mucopolysaccharidosis (phase 2).

Forward Looking Statements

This Company announcement contains forward-looking statements, including statements

regarding anticipated commencement dates or completions dates of nonclinical or clinical

trials, regulatory developments, and regulatory approval. These forward-looking

statements are not guarantees or predictions of future performance, and involve known

and unknown risks, uncertainties, and other factors, many of which are beyond our

control, and which may cause actual results to differ materially from those expressed in

the statements contained in this presentation. Readers are cautioned not to put undue

reliance on forward-looking statements.

To learn more please visit: https://paradigmbiopharma.com

Approved for release by the Paradigm Board of Directors.

FOR FURTHER INFORMATION PLEASE CONTACT:

Simon White

Director of Investor Relations

Tel: +61 404 216 467

Paradigm Biopharmaceuticals Ltd

ABN: 94 169 346 963

Level 15, 500 Collins St, Melbourne, VIC, 3000, AUSTRALIA

Email: investorrelations@paradigmbiopharma.com

long term this announcement is important as further confirmation that the drug works and will be approved (sooner or later)

short term I think this will be a catalyst for the SP to recover having been pummeled as part of the pre-revenue blow up and risk off environment.

still need to watch cashburn but hopefully the scariest times are behind

This is a little scary. The cashburn is so significant that even with nearly 60 mil in the bank they’re looking at less than 4 quarters of cash…

unfortunately I can see this leading to sag in SP which then makes the cash raise more dilutive… the question as an investor then is do you sell down some knowing there’s a raise coming? I still believe in the product and think this will be profitable long term…

only 10k but I guess it’s better than nothing

Appendix 3Y Change of Director’s Interest Notice

Rule 3.19A.2

Information or documents not available now must be given to ASX as soon as available. Information and documents given to ASX become ASX’s property and may be made public.

Introduced 30/09/01 Amended 01/01/11

Name of entity Paradigm Biopharmaceuticals Limited ABN 94 169 346 963

We (the entity) give ASX the following information under listing rule 3.19A.2 and as agent for the director for the purposes of section 205G of the Corporations Act.

Name of Director  Helen Fisher Date of last notice  26 February 2021

Part 1 - Change of director’s relevant interests in securities

In the case of a trust, this includes interests in the trust made available by the responsible entity of the trust

Note: In the case of a company, interests which come within paragraph (i) of the definition of “notifiable interest of a director” should be disclosed in this part.

Appendix 3Y Change of Director’s Interest Notice

   Direct or indirect interest

Date of change

No. of securities held prior to change

Class

Number acquired Number disposed

Value/Consideration

Note: If consideration is non-cash, provide details and estimated valuation

No. of securities held after change

+ See chapter 19 for defined terms. 01/01/2011 Appendix 3Y Page 1

Direct

18 May 2023 Nil

Ordinary Shares 10,204

Not applicable $10,020

10,204 Fully Paid Ordinary Shares

 Nature of indirect interest

(including registered holder)

Note: Provide details of the circumstances giving rise to the relevant interest.

  Not applicable

Appendix 3Y

Change of Director’s Interest Notice

Part 2 – Change of director’s interests in contracts

Note: In the case of a company, interests which come within paragraph (ii) of the definition of “notifiable interest of a director” should be disclosed in this part.

 Nature of change

Example: on-market trade, off-market trade, exercise of options, issue of securities under dividend reinvestment plan, participation in buy-back

  On-market trade

 Detail of contract Nature of interest

Name of registered holder (if issued securities)

Date of change

Interest acquired

Interest disposed

Value/Consideration

Note: If consideration is non-cash, provide details and an estimated valuation

Interest after change Part 3 – +Closed period

Not applicable Not applicable

Not applicable Not applicable

Not applicable Not applicable Not applicable

Not applicable

    No. and class of securities to which

interest related prior to change

Note: Details are only required for a contract in relation to which the interest has changed

  Not applicable

      Were the interests in the securities or contracts detailed No above traded during a +closed period where prior written

 clearance was required?

If so, was prior written clearance provided to allow the trade to proceed during this period?

If prior written clearance was provided, on what date was this provided?

+ See chapter 19 for defined terms. Appendix 3Y Page 2

Not applicable Not applicable

    01/01/2011

Paul Rennie who knows the business better than anybody just bought 70k shares in market.

#stillbullish

Appendix 3Y Change of Director’s Interest Notice

Rule 3.19A.2

Information or documents not available now must be given to ASX as soon as available. Information and documents given to ASX become ASX’s property and may be made public.

Introduced 30/09/01 Amended 01/01/11

Name of entity Paradigm Biopharmaceuticals Limited ABN 94 169 346 963

We (the entity) give ASX the following information under listing rule 3.19A.2 and as agent for the director for the purposes of section 205G of the Corporations Act.

Name of Director  Paul Rennie

Date of last notice  22 December 2022

Part 1 - Change of director’s relevant interests in securities

In the case of a trust, this includes interests in the trust made available by the responsible entity of the trust

Note: In the case of a company, interests which come within paragraph (i) of the definition of “notifiable interest of a director” should be disclosed in this part.

Direct or indirect interest Direct and indirect interest

Date of change 12 May 2023

Appendix 3Y Change of Director’s Interest Notice

    Nature of indirect interest

(including registered holder)

Note: Provide details of the circumstances giving rise to the relevant interest.

  Mr Paul Rennie is the legal and beneficial owner of 100% of the securities in KZEE Pty Ltd.

Mr Paul Rennie is the legal and beneficial owner of 100% of the securities in EAR Investments Pty Ltd.

   + See chapter 19 for defined terms. 01/01/2011 Appendix 3Y Page 1

Appendix 3Y

Change of Director’s Interest Notice

 No. of securities held prior to change

  Paul Rennie

– 8,426,697 Fully Paid Ordinary Shares

KZEE Pty Ltd ATF KZEE Superannuation Fund

– 10,914,902 Fully Paid Ordinary Shares registered in the name of KZEE Pty Ltd. Mr Paul Rennie is the legal and beneficial owner of 100% of the securities in KZEE Pty Ltd.

EAR Investments Pty Ltd ATF EAR Investments Trust

– 1,097,355 Fully Paid Ordinary Shares registered in the name of EAR Investments Pty Ltd. Mr Paul Rennie is the legal and beneficial owner of 100% of the securities in EAR Investments Pty Ltd.

Total No. of shares held after change

– 20,438,954 Fully Paid Ordinary Shares

  Class

Number disposed

Ordinary Shares

Not applicable

Number acquired

  Paul Rennie

– 73,851 Fully Paid Ordinary Shares

  Value/Consideration

Note: If consideration is non-cash, provide details and estimated valuation

  Paul Rennie

– $76,001

  + See chapter 19 for defined terms. Appendix 3Y Page 2

01/01/2011

Detail of contract Nature of interest

Name of registered holder (if issued securities)

Date of change

Interest acquired Interest disposed

+ See chapter 19 for defined terms. 01/01/2011 Appendix 3Y Page 3

Not applicable Not applicable

Not applicable Not applicable

Not applicable Not applicable

Appendix 3Y Change of Director’s Interest Notice

 No. of securities held after change

  Paul Rennie

– 8,500,548 Fully Paid Ordinary Shares

KZEE Pty Ltd ATF KZEE Superannuation Fund

– 10,914,902 Fully Paid Ordinary Shares registered in the name of KZEE Pty Ltd. Mr Paul Rennie is the legal and beneficial owner of 100% of the securities in KZEE Pty Ltd.

EAR Investments Pty Ltd ATF EAR Investments Trust

– 1,097,355 Fully Paid Ordinary Shares registered in the name of EAR Investments Pty Ltd. Mr Paul Rennie is the legal and beneficial owner of 100% of the securities in EAR Investments Pty Ltd.

Total No. of shares held after change

– 20,512,805 Fully Paid Ordinary Shares

 Nature of change

Example: on-market trade, off-market trade, exercise of options, issue of securities under dividend reinvestment plan, participation in buy-back

  On-market trade

  Part 2 – Change of director’s interests in contracts

Note: In the case of a company, interests which come within paragraph (ii) of the definition of “notifiable interest of a director” should be disclosed in this part.

    No. and class of securities to which interest

related prior to change

Note: Details are only required for a contract in relation to which the interest has changed

  Not applicable

Appendix 3Y

Change of Director’s Interest Notice

Value/Consideration

Note: If consideration is non-cash, provide details and an estimated valuation

Interest after change Part 3 – +Closed period

Not applicable Not applicable

    Were the interests in the securities or contracts detailed No above traded during a +closed period where prior written

 clearance was required?

If so, was prior written clearance provided to allow the trade to proceed during this period?

If prior written clearance was provided, on what date was this provided?

Not applicable Not applicable

    + See chapter 19 for defined terms. Appendix 3Y Page 4

01/01/2011

I have little doubt that zilosul (pentosan polysulphate) has a meaningful effect on OA within the e knee…

if the business is able to transform this pharmacology into any meaningful slice of the OA analgesia market at all it will be worth many multiples of its current market cap…

the cashburn in the most recent year, however, was ~30 mil with about 70 mil sitting in the bank…

whilst I’m hoping it was a costly half because of the roll out of the pivotal trial km realistic enough to expect ongoing costs of a similar magnitude…

the way out? A big pharma buy out or partnership triggered by the release of promising results this year… or ANOTHER cap at a pretty sub optimal time with respect to macro conditions…

watch this space …

disclosure held IRL and clearly in SM

Just a quick thought on announcements re the R & D tax concession. There is no doubt it is a material Ann, but let's be realistic, it's free kick from the ATO and like all tax rebates, you have to spend a chunk to get a smaller chunk back.

Most larger companies now use this to capitalise tax losses. My view is the only real issue is how much did they get, thereby how much did they spend, how much "bodgy" cross charges went in and how much real R & D got done. If it's a tech or bio company that lives and breaths based on continuing R & D then has to be seen as positive. Quite frankly, some companies R & D, I suspect produce little benefit to revenue or profits going forward.

Has anyone else noted the share price run from a low of 85.5 cents at end of June to a current SP of 1.52 on essentially no news!

What a great example of the market being there to serve and not to inform!

Or am I missing something?

approval for UK and Canada recruitment to pivotal phase 3 trial given.

just expected progress but better than the alternative

ASX RELEASE 6th July 2022

Paradigm reports important global progress for the PARA_OA_002 phase 3 clinical trial evaluating Zilosul® for osteoarthritis.

KEY HIGHLIGHTS

• Regulatory and ethics approval are in place for the UK. The first UK screening site for the phase 3 study is now active, enabling Paradigm to commence screening and enrolling participants.

• Regulatory approval for the Para_OA_002 phase 3 trial has been granted by Health Canada

is pleased to announce it has activated the first trial site in the UK. The Company has received UK regulatory and ethics approvals to proceed with the Para_OA_002 phase 3 clinical trial evaluating knee osteoarthritis (OA). Now that the first site is activated in the UK participant screening and enrolment will begin imminently. This first site is located at the University of Leeds under lead investigator Prof. Hemant Pandit. Paradigm aims to activate a total of seven sites across the UK for the phase 3 study. The remaining sites will be activated in the coming months.

Paradigm is also pleased to announce that the global PARA_OA_002 phase 3 osteoarthritis clinical trial has regulatory approval from Health Canada. An ethics submission has been made to the research ethics board in Canada, with approval pending. Once ethics approval has been granted, Paradigm will activate clinical sites to begin participant screening and enrolment for the phase 3 study. Paradigm plans to activate up to 10 sites across Canada.

Paradigm’s phase 3 trial now has regulatory approvals to proceed from the US FDA, the UK Medicines and Healthcare products Regulatory Agency (MHRA), Health Canada, and the Australian TGA. Recruitment milestones will be announced as they are achieved.

Dr Donna Skerrett, Paradigm CMO commented: “I am pleased we are moving forward with regulatory approval within another planned jurisdiction for the global phase 3 program. The interaction with Health Canada was positive throughout the regulatory process and the Company looks forward to announcing anticipated ethics approval and subsequent participant recruitment in Canada. Equally, the achievement by the Paradigm team to activate participant recruitment in the UK highlights Paradigm's ongoing execution of activities for this global phase 3 trial in knee OA.”.

ASX RELEASE 17th March 2022

Paradigm has received regulatory and ethics approvals for the

PARA_OA_002 clinical trial in the UK.

KEY HIGHLIGHTS

• Regulatory and ethics approval has been received from the Medicines and

Healthcare products Regulatory Agency (MHRA) in the United Kingdom

(UK).

• Paradigm now has all the required approvals in place to commence clinical

trial site activation in the UK for PARA_OA_002.

• Paradigm was granted permission to become part of the pilot test phase

rollout of the combined regulatory and ethics applications, thereby reducing

both time and costs.

• 5 sites in the UK are planned for initiation and activation to enrol participants

with knee OA into the PARA_OA_002 study.

Paradigm Biopharmaceuticals Ltd (ASX: PAR) (“Paradigm” or “the Company”), a

clinical stage biopharmaceutical company focussed on repurposing existing molecules

for new indications with unmet clinical needs, is pleased to announce it has received

regulatory and ethics approval from the MHRA in the UK. Paradigm now has all the

required approvals in place to commence clinical trial activities in the UK for its global

Phase 3 PARA_OA_002 clinical trial and expects to imminently commence enrolling

participants with knee OA into the PARA_OA_002 study in 5 sites in the UK.

The recent approval of phase 3 trials by the FDA for a pivotal trial for pentosan polysulphate in OA could be the catalyst for an uptick in stock price. More importantly, I believe the trial will confirm that this is a safe and effective drug for OA. This alone would justify a massive valuation given the TAM, however the 008 trial looking at disease modification may boost the value further. The variant perception here I believe is the likelihood of success in the recently approved phase 3 trial. There is a lot of data to suggest the drug works and also basic science evidence as to the mechanism. I think the stock is more de-risked than the market gives it credit for.

Paradigm Biopharmaceuticals Ltd (ASX: PAR) (Paradigm or the Company), wishes to inform the market it has received a written response from the US FDA in relation to its Investigation New Drug (IND) submission for pentosan polysulfate sodium (PPS) to treat pain in subjects with knee Osteoarthritis.

In response to the FDA's one request, Paradigm will make an amendment to Its protocol. Response received from the US FDA. The one outstanding question regarding adrenal gland function related to a preclinical finding in the adrenal gland of rats only and was not seen in the adrenal gland of dogs. Adrenal gland malfunction has not previously been seen by Paradigm or bene pharmaChem in their ongoing pharmacovigilance. This one preclinical finding has been the focus of the ongoing US FDA review.

Paradigm, working with external endocrinologists, presented changes to the clinical trial protocol, which included a comprehensive adrenal screening protocol and clinical monitoring as part of its mitigation plan. In the written communication, the FDA requested modifications to Paradigm’s adrenal screening and mitigation plan. Paradigm plans to amend its clinical trial protocol, including all the FDA’s requests, and respond to the FDA within the next week.

Paradigm assumes the FDA may again take 30 days to respond. Mr Paul Rennie, Paradigm Chief Executive Officer: “Although we understand the agency's obligations for thorough reviews which commenced in March of this year, I am confident that the FDA and Paradigm have now attained a pathway to commence our phase 3 clinical trial in the US”.

***

Another month and another month's delay.  At least the FDA didn't take the full 30 days to respond this time.  Hopefully this is it though and we'll get approval to proceed in October.  [Drums fingers on desk].

[Held]

Thanks for bringing this to my attention. I had a patient who was a racehorse owner with terrible arthritis.

He had noticed the amazing effect it had on his animals and had somehow managed to convince the vet that looked after his racehorses to let him have " a couple of extra vials" in case they lost some. 
He swore he was a new man since injecting himself with Cartrofen and was convinced there was some big pharma conspiracy as to why it wasn't available to humans!

id completely forgotten about it til now!

EDIT: This is in no way an endorsement of this drug, and absolutely not a suggestion to start injecting yourself with equine products. Furthermore anecdotes are in no way proof.  This was just a funny story I thought I'd share!

26-Apr-2021:  PARADIGM PROVIDES IND APPLICATION UPDATE

Not sure why CAPITAL LETTERS were required in that announcement title.  Did not think it was worth shouting about.  Perhaps the company secretary just had an extra couple of Weetbix this morning...

INVESTIGATIONAL NEW DRUG (IND) APPLICATION UPDATE

Paradigm Biopharmaceuticals Ltd (ASX: PAR), a clinical stage biopharmaceutical company focussed on repurposing existing molecules for new indications with unmet clinical needs, reports today an update on its IND application to the US Food and Drug Administration (FDA) for the proposed pivotal clinical trial treating subjects with pain associated with Knee Osteoarthritis (OA).

Paradigm previously reported it submitted its over 30,000-page IND application to the US FDA, Friday 26th March 2021, and to date Paradigm has received few questions from the FDA during the current 30-day IND review period. Those few questions were answered by Paradigm within 48 hours of receipt.

On Friday April 23, Paradigm received a verbal indication from the FDA that the FDA would be putting further questions to Paradigm outside the 30-day IND review period. The FDA was unable to provide all questions within the initial IND review period and has advised it will submit them to Paradigm within the next 30 days. Many of the questions which, as we understand from the brief discussion with the FDA, are related to newly submitted non-clinical data (as part of the IND application).

Paradigm is ready to review and answer questions when they are received. Once in receipt of Paradigm’s responses, the FDA will review within 30 days.

Paradigm is committed to keeping investors up to date with our development program and will update the timeline once we receive clarity.

--- ends ---

Summary:

FDA:  Coupla questions, some now, some later...

PAR:  Bring it ON!!!

About Paradigm Biopharmaceuticals

Paradigm Biopharmaceuticals LTD (ASX: PAR) is a late-stage drug development company with the mission to develop and commercialise Pentosan Polysulfate Sodium (PPS) for the treatment of pain associated with musculoskeletal disorders driven by injury, inflammation, aging, degenerative disease, infection or genetic predisposition.

[I hold PAR shares.  Warning:  While this is indeed a "late stage" drug development company that is seeking to repurpose a drug that has already got EU approval for use as an antithrombotic medication, the FDA approval remains a binary equation.  Either they will get it, or they won't.  If they do, there is clearly substantial upside.  If they don't there is clearly substantial downside, particularly in terms of their share price.  That is why my PAR position is a very small one.  Never bet more than you can afford to lose on such companies, because if things do not go the way they hope, they can easily go to zero.  The value is all in the potential, and the potential can be easily wiped out with one solid knockback by a regulatory authority as powerful as the FDA.]

31-July-2020:  Quarterly Activities Report

[I hold PAR shares]

30-Apr-2020:  EAP treatment completed and Orphan Status achieved for MPS-I

Paradigm reports:  Under the US FDA Expanded Access Program (EAP) treatment is completed for all of the ten planned patients. Paradigm granted Orphan Status by US FDA for MPS-I 
 
KEY HIGHLIGHTS:  

• Total Patient population (n=10) have completed dosing with Zilosul® (iPPS) in the US under the US IND Expanded Access Program (EAP).
• The Expanded Access Program remains on-track with patients completing scheduled checkups out to 6 weeks post final injection (Day 83). 
• Paradigm expects to report results for the entire patient population (n=10) to the market Q3 CY2020. 
• Patient data reported will be in line with primary and secondary endpoints for the proposed Phase 3 trial.
• FDA has granted Paradigm orphan designation request for treatment of MPS-I complications - including pain and arthropathy.

Paradigm Biopharmaceuticals Ltd (ASX: PAR) is pleased to announce it has completed treatment of all ten patients with Zilosul® under the FDA IND Expanded Access Program (EAP) in the US. The company has also been advised by the FDA that Paradigm’s orphan designation request for MPSI has been granted, joining the previously granted designation for MPS-VI.

The EAP which commenced on the 18th February with the treatment of the first patient, has now treated all of the ten planned patients. All patients taking part in the study must complete regular evaluations with the treating physician, with the final evaluation taking place 6 weeks post the last injection received (day 83). The EAP program will report on pain outcomes similar to those previously evaluated in the TGA SAS (refer ASX Announcement 6th April) as well as those proposed as endpoints for the Phase 3 Clinical trial. Paradigm expects data for the total population (n=10) of patients to be available to the market during Q3 CY 2020. 

Mr. Paul Rennie, Paradigm’s Chief Executive Officer said: “Paradigm is excited to have achieved this milestone, especially during the current health conditions created by COVID-19 and would like to thank all those involved in the Expanded Access Program for their continued diligence to the treatment program."

--- click on the link above for more, including:

• What is The FDA Expanded Access Program?
• Mucopolysaccharidosis type 1 (MPS-I) – Orphan Status
• What is MPS? 

About Injectable PPS (iPPS):  Injectable PPS (iPPS) is not currently registered in Australia, but it is was previously registered in four of the seven major global pharmaceutical markets. In those European markets, iPPS is registered as an antithrombotic agent. In Australia, iPPS for human use is not currently available for sale. 
 
Zilosul® is a registered Trademark of Paradigm Biopharmaceuticals Ltd (ASX: PAR). 

[Disclosure:  I hold PAR shares.]

14/02/2020: Half Yearly Report and Accounts

If I'm reading this right, PAR is making a loss but less of a loss than previous QTR.

Interested to see how the market responds on Monday.