Investor presentation gives an indication of next milestones with Clinical trial results from diabetic foot ulcer in early 25 and aGvHD trial in 2H25. The DFU trial interim results looked positive enough for CYP to buy the IP for the dressing technology rather than license.

Cynata entered into a worldwide exclusive license agreement with TekCyte to use this technology, which is based on proprietary surface modification techniques, to produce polymer-coated dressings for the delivery of MSCs to wounds.

Cynata will issue shares to the value of $230,000 to TekCyte.

Patient enrolment in the DFU trial has been completed (announced 8 April 2024), and initial results are promising. An analysis of the first 16 patients enrolled after 10 weeks’ follow-up showed a median percentage reduction in wound surface area of 87.6% in the active CYP-006TK group, compared to 51.1% in the control group (announced 26 February 2024).

Dr Kilian Kelly, Cynata’s CEO and Managing Director, said: “Ownership of this technology strengthens our intellectual property position and simplifies our commercial proposition for potential partners. We are very excited by the initial results in our trial of CYP-006TK in DFU, and optimistic about the potential for this product to meaningfully change outcomes for patients.”

Small holding in RL

Listening to New Scientist weekly podcast an interesting segment on placental cells being used for heart repair following a study from Mount Sinai showing stem cells derived from the placenta known as Cdx2 cells can regenerate healthy heart cells after heart attacks in animal models.

Back in September 22 CYP announced: Cynata Therapeutics is set to investigate its Cymerus mesenchymal stem cells (MSCs) as a treatment for ischaemic heart disease (IHD) thanks to a $1 million grant from the Australian government.

The perception of stem cells took a hit when MSB was knocked back by the FDA for a second time with a request for further clinical trials.

CYP announced approval for a clinical trial in kidney transplant recently and has opened recruitment for its phase 2 clinical trial in aGvHD a treatment for the rejection of bone marrow transplants for blood diseases.

Stem cells continue to show potential. CYP's MSC have scalability and uniformity of production. The placental stem cells seem to have the advantage of not causing rejection.

Commercial use still a long way off but a small hold in RL following this interesting technology.

Things have been pretty quiet re the company and the SP has suffered. Now a CR at 21.5c to finally progress the GVHD trial.

Cynata is currently finalising contractual and logistic arrangements with individual sites (hospitals) to prepare for patient recruitment. This approval follows the landmark clearance by the US FDA of Cynata’s Investigational New Drug (IND) application in 2022, the grant of Orphan Drug Status for CYP-001 and Institutional Review Board (IRB) approval in the United States.

The proposed clinical trial titled “A Multicenter, Randomized, Double-blind, Placebo-Controlled Phase 2 Study to Investigate the Efficacy and Safety of CYP-001 in Combination with Corticosteroids vs Corticosteroids Alone for the Treatment of High-Risk Acute Graft Versus Host Disease” is expected to be conducted in approximately 60 patients at sites across the U.S., Europe and Australia.

Cynata has received firm commitments for a A$5.0 million Placement at an offer price of $0.215

• The Placement was cornerstoned by specialist healthcare fund and existing investor Bioscience Managers and was supported by new and existing institutional shareholders and Cynata’s senior management and Board members

• Proceeds will be used to fund the Company’s clinical program including the proposed Phase 2 clinical trial in acute graft-versus-host disease (aGvHD)

• In addition to the Placement, Cynata will offer all eligible shareholders the opportunity to participate in a Share Purchase Plan which will be capped at $2.0m

• Placement and SPP shares offered with free attaching options on a 1:2 basis, exercisable at $0.30 and expiring on 1 April 2025

• Post transaction the Company’s pro forma cash balance will be $21m. This will support the Company’s clinical programs through several key catalysts and into FY25

Held in RL and will top up through the SPP. Long term investment and very speculative.

Hard to get excited about future focused announcements in the current market but Cynata’s tech use in $1M grant into cell treatment for heart damage from heart attack further supports the technology.

The project is expected to run for a period of two years. It will involve encapsulating Cymerus MSCs in a clinical grade device which can be implanted below the skin (subcutaneously) to allow sustained delivery of the bioactive molecules released by the MSCs. Aims of the project include optimisation of the encapsulation approach, and demonstration of long-term cardiac repair in rat and sheep models of acute myocardial infarction, i.e. heart attack. If successful, it is anticipated that these studies would support progression to human clinical trials.

Key Highlights:

• Medical Research Future Fund (MRFF) has awarded St Vincent's Institute of Medical Research, Melbourne (SVIMR) a ~$1m grant to investigate Cynata’s mesenchymal stem cells (MSCs) in ischaemic heart disease (IHD)

• IHD is the leading cause of heart failure and death worldwide: there is an urgent need for new therapeutic strategies

• Cynata to partner with multiple leading research institutions on this project, which will be led by SVIMR

• Cynata’s CymerusTM MSCs have been shown to have multiple positive effects in a preclinical model of IHD/heart attacks

• This project will focus on an innovative and minimally invasive method to harness the effects of MSCs in a sustained manner, to provide long-term cardiac reparative effects

Wound Awareness week has seen some media on radio and web stories (behind paywall). Department of Health and Aged care studying wound consumables and reporting to federal govenrment June 2023 could expand the market for CYP or PNV who are also conducting a Diabetic Foot Ulcer trial

CYP mentioned in the Adelaide advertiser (paywall) details of the collaboration with University of Adelaide and Adelaide company Tekcyte product Cypatch

Breakthrough could treat thousands of people with chronic wounds

An Adelaide breakthrough in healing chronic wounds with a special dressing has an extraordinary pedigree – a single donor generating “limitless” regenerative stem cells.

ABC online Chronic wounds affect 420,000 Australians each day, cost $3b a year to treat

AMA vice president Danielle McMullen said the analysis in the report showed a $23.4 million investment in preventing and treating chronic wounds would yield a $203 million benefit over four years.

"I don't know of many investments where for every $1 you spend, the return is $8.36, but this is the case with evidence-based wound care," she said. 

Dr McMullen said one huge cost was for special dressings for open wounds, like those that could have helped Thomas when he first arrived at the country hospital.

She said while they were free for patients in hospitals, someone had to pay for them if they were used in a GP clinic. 

"At the moment, Medicare doesn't cover the cost of the dressings we need to treat chronic wounds correctly," she said.

"So doctors are either bearing the costs themselves or are forced to pass on the cost to patients, and that’s not something we like doing."

She said that created an incentive for patients to go through the hospital system, not their local GP, which the AMA claims is more expensive than treating someone in a GP clinic. 

The AMA report quotes a 2013 study that found patients over 60 with venous leg ulcers were spending $27.5 million on dressings alone. 

The association is also calling for a new Medicare rebate that applies to practice nurses, Aboriginal and Torres Strait Islander health practitioners and Aboriginal health workers treating and cleaning wounds.

Under the existing rebate scheme, a GP needs to be in the room in order for a rebate to be claimed — even if the nurse or health worker does all the work. 

In a statement, the Department of Health and Aged Care said it was studying "wound consumables" such as dressings, with results to be sent to the federal government in June next year. 

The department said this directly addressed one of the recommendations from the AMA and Wounds Australia. 

It also said that implementing recommendations from the Royal Commission into Aged Care Quality and Safety would improve wound care for older Australians. 

Disc: Hold CYP in RL and PNV in RL and SM

CYP 4C FDA approval for GvHD phase 2, delays to phase 3 trials, plenty of cash at hand.

FDA approves Cynata’s IND application for Phase 2 trial in aGvHD

This is a major value catalyst for the Company as it provides a development and commercialisation gateway into the USA, not only for aGvHD but potentially for further clinical targets.

The results of the primary evaluation are expected in early 2024. The trial aims to recruit 60 patients with high risk aGvHD across a number of countries including the USA and Australia with patient Overall Response Rate (ORR) evaluated at Day 28. Participants will be randomised and will receive either CYP-001 or a placebo, in addition to corticosteroids, the current standard-of-care.

Progress continues to be made in the Phase 3 trial in osteoarthritis with patient enrolment steadily advancing. The Phase 3 trial is the largest randomised controlled trial of MSCs conducted in patients with osteoarthritis worldwide, with results having the potential to disrupt clinical management of OA patients, globally. The sponsor of the study, the University of Sydney, had expected the trial to conclude in late 2024, but that forecast is presently under review based on the current recruitment ratee.

The MEND respiratory distress clinical trial is ongoing with completion expected later this year. The addition of St George Hospital as a new site for MEND clinical trials will help to streamline and accelerate the recruitment process.

Cynata’s clinical trial in DFU comprising 30 adult patients is expected to report in the first half of calendar 2023. Cynata is actively seeking to address the slow rate of recruitment, caused largely by the well-publicised crisis in the hospital system in Australia, through multiple mitigation strategies.

Cynata’s core focus is to complete recruitment in its active clinical trials, navigate the beginning of its Phase 2 clinical trial in aGvHD with study centres and other stakeholders, and to continue engagement in commercial discussions with multiple potential partners.

Cynata closed the quarter with A$23.8m in cash, as at 30 June. Net operating cash outflows for the quarter totalled A$2.27m, primarily relating to a small reduction in research and development expense

US Patent Use of the Cymerus™ MSCs in Asthma strengthens IP in US.

Notice of Allowance has been received from the United States Patent and Trademark Office (USPTO) for a patent application covering the use of its proprietary Cymerus™ mesenchymal stem cell technology in treating asthma and allergic airways disease (AAD).

Cynata anticipates that the patent will be granted around October 2022, with an expiration date of 31 August 2038.

Clinical trials of Cymerus products in osteoarthritis, respiratory failure and diabetic foot ulcers (DFU) are currently ongoing. In addition, Cynata has demonstrated utility of its Cymerus technology in preclinical models of numerous diseases, including the clinical targets mentioned above, as well as critical limb ischaemia, idiopathic pulmonary fibrosis, asthma, heart attack, sepsis, acute respiratory distress syndrome (ARDS) and cytokine release syndrome.

Early stage stem cell treatment study for lung disease supporting CYP's MSC stem cells. Shows how long the timelines are for Biotech with COVID delays as the study was announced in March 21. Not enough to change the share price but continues to support stem cell treatment progression.

Pre-clinical Study of Lung Disease Supports High Potency of Cynata’s Cymerus™ MSCs

Key Highlights: • Pre-clinical study in an animal model of idiopathic pulmonary fibrosis (IPF), a serious lung disease, identifies molecular basis for high potency of Cynata’s Cymerus mesenchymal stem cells (MSCs)

Treatment with Cymerus MSCs significantly ameliorated the mediators of lung inflammation in the model at the same time as promoting anti-inflammatory effects

Provides further evidence supporting the potent effects of Cymerus MSCs in bleomycin induced inflammatory lung disease • Outlines the mechanisms of action by which Cymerus MSCs provide therapeutic efficacy as a potential treatment option for idiopathic pulmonary fibrosis (IPF)

Reduced cash outflow, trials progressing slowly due to COVID restrictions / delays.

Net operating cash outflows for the quarter totalled A$1.23m, primarily relating to the receipt an A$833k R&D Tax Incentive Rebate and a reduction in research and development expenses (as a consequence of the cyclic nature of R&D expenditure) of $1.83m

Strong financial position with A$25.28m in cash as at 31 March 2021

The Phase 3 osteoarthritis trial is the largest randomised controlled trail of MSCs conducted in patients with osteoarthritis worldwide, and so the results have the potential to have a major impact on clinical management of OA patients, globally. The sponsor of the study, the University of Sydney, expects the trial to conclude in 2024, as planned. 

Cynata expects to complete recruitment of 24 patients in the MEND respiratory distress trial and 30 patients in the DFU trial by the end of the calendar year.

Further important IP protection and interesting note about ongoing engagement with potential partners.

Cynata Receives Cynata Receives Notice of Decision to Grant a Patent from Chinese Patent Office 

Dr Ross Macdonald, Cynata’s Chief Executive Officer, said: “This wholly Cynata-owned patent encompasses novel aspects of the manufacturing process of Cynata’s Cymerus MSC products and joins an extensive list of issued patents protecting our unique and proprietary IP. China is an enormously important market as its economy continues to grow and the central government accelerates the pace of adoption of sophisticated, cutting-edge medicines. This achievement will be of significant assistance in our ongoing engagement with potential partners in China. The Cymerus platform enables manufacture of consistent, high-quality MSCs at scale. This unique and valuable characteristic of Cynata’s technology is key to the development of off-the-shelf therapeutic stem cell products to target a range of devastating diseases worldwide”

Cynata Receives Decision to Grant a Patent in Japan.

Decision to Grant a Patent has been received from the Japanese Patent Office (JPO) for a patent application covering its proprietary CymerusTM mesenchymal stem cell technology. The patent application entitled “Pluripotent Stem Cell Assay” is wholly-owned by Cynata.

Dr Ross Macdonald, Cynata’s Chief Executive Officer, said:

“This further patent, which is wholly-owned by Cynata, describes an important analytical procedure to assure the quality and uniformity of Cynata’s Cymerus MSC products. It builds on our already comprehensive patent portfolio to protect our unique and proprietary IP. Of particular relevance is the fact that this achievement is in Japan, the second largest market for pharmaceutical products and the leading country in regenerative medicine.

ArK has just increased its position in Fate Therapeutics (FATE) with similarities to CYP which starts its Diabetic Foot Ulcer trial. Increasing the acceptance of stem cell treatment?

The novel approach uses human induced pluripotent stem cells (iPSC) to create a precisely engineered immunotherapy with unlimited production of cells – and not depended on the patient as a source for initial cells. The result is reliable, homogenous product forms to attack specific cancers and disease conditions.

Cynata Commences DFU Clinical Trial

The Phase I trial (protocol number CYP-DFU-P1-01) aims to recruit 30 adult patients with DFU who will be randomly assigned to receive CYP-006TK or standard care of treatment. CYP-006TK is a novel polymer-coated silicon wound dressing seeded with CymerusTM mesenchymal stem cells (MSCs) to facilitate topical application to the wound. Cynata has exclusively licensed the dressing technology from leading manufacturer of innovative biomedical coatings, TekCyte Limited.

The trial will take place at Royal Adelaide Hospital and The Queen Elizabeth Hospital, Adelaide, Patients will receive study treatment for a period of 4 weeks, evaluation will continue for a total of 24 weeks. The primary outcome measure in the trial will be safety, while secondary outcome measures will include wound healing, pain and quality of life at 12 and 24 weeks after treatment initiation. Cynata currently expects to complete the trial during the 2022 calendar year.

Dr Kilian Kelly, Cynata’s Chief Operating Officer, said:

“Commencing the first human trial is a major milestone in the development of any new product, and we are pleased to have achieved this for our DFU program prior to the end of the year as projected. We look forward to evaluating the effects of this novel treatment on DFU, which are a debilitating and potentially limb or even life-threatening chronic complication of diabetes.”

Rat study shows potential of stem cell treatment in repairing damage to heart muscle from heart attacks. This gives another application following the Nature article in Nov 2020.

Still a long way from general market but significant potential. CYP’s advantage is the single source rather than individual donor cells which allows large scale production and standardisation for trials.

Preclinical Study Showing Beneficial Effects of CymerusTM MSCs in Heart Attacks Published in Leading Peer-Reviewed Journal 

Cells were injected into the wall of the heart. The results were positive and demonstrated the efficacy of Cymerus MSCs in this model of myocardial infarction.

iPSC-derived MSCs offer an exciting opportunity for an “off-the- shelf” stem cell therapy for cardiac repair, due to their consistency and manufacturing scalability.”

Key Results

• Cymerus MSCs (p=0.01), but not bone marrow-derived MSCs (p=0.63), significantly enhanced left ventricular cardiac function.

 • Both Cymerus MSCs (p=0.001) and bone marrow-derived MSCs (p=0.003) significantly increased the number of new capillaries (very small blood vessels between arteries and veins) in the damaged area of the heart.

• Cymerus MSCs (p<0.0001), but not bone marrow-derived MSCs (p=0.09), significantly increased the number of new arterioles (the smallest branches of arteries) in the damaged area of the heart.

• The beneficial effects of Cymerus MSCs in this model appear to result from the release of molecules that stimulate new blood vessel growth, rather than engraftment of the MSCs or reduction in the size of the scar in the heart muscle. Notably, the levels of relevant molecules released by Cymerus MSCs were up to two to four times as high as those released by bone marrow-derived MSCs.

• Administration of MSCs was found to be safe, and did not cause irregular heart rhythms.

Still a long road ahead to any meaningful cash flow.

Revenue drops from 7.1M(2020) to 1.7M but 4.5M was the licensing fee from FujiFilm for GvHD.

Loss increases from 3.6M to 7.7M

Shares increase from 104M to 130M

26M in cash having raised 18M so well funded for continuation of trials

Product development costs down from 5.9M to 3.8M

Net cash outflow 5.1M vs 3.4M

GvHD

“Cynata continues to collaborate on the planning and start-up activities in preparation for a proposed Phase 2 clinical trial. The company remains in active discussions with FUJIFILM, noting that responsibility for development and commercialisation lie with FUJIFILM.”

Still recruiting for Osteoarthritis trial (no numbers given) externally funded

Respiratory failure trial only mentions one patient in May21

Diabetic foot ulcer trial in Q4 21

No details of license fee for TekCyte, planning for trial underway.

idiopathic pulmonary fibrosis (IPF) and potential trial in renal transplantation.

“We continue to liaise with Fujifilm on the licensed GvHD program, while actively exploring other licensing and partnership agreements as we look towards commercialisation opportunities for our other portfolio products. The worldwide exclusive licence agreement signed this year with biomedical coating manufacturer TekCyte for the proposed trial in diabetic foot ulcers enables exclusive use of TekCyte’s unique polymer-coated dressings in this clinical trial and, if clinical development is successful, ultimately to commercialisation. These agreements and partnerships will help drive valuable commercial outcomes for Cynata.”