Syntara (SNT: $0.33) is developing its antifibrotic drug candidate portfolio for a range of conditions. Recently the company announced that its skin scar treatment compound was safe, and detailed an excellent Phase Ib study design aimed at delivering rapid, objective efficacy data under placebo control.
The company is aiming to bring to market the first scar treatment pharmaceutical that treats the underlying biology of the disease. Its previous study had two flaws. The first was that it was assessed on very mature scars with an average age of 13 years. The second is that the drug candidate produced some minor skin reactions, which was not ideal. However a 30% reduction in collagen levels was achieved in the scars plus an increase in vascularisation.
To address these two issues, Syntara has developed an improved formulation of the first compound, which it has labelled SNT-9465 (previous formulation is called SNT-6302). That compound just passed the Phase Ia safety study with an acceptable safety profile. It also showed that target inhibition (LOX) was achieved in a dosed dependent manner. Importantly the drug compound does not just block one of the LOX pathways for collagen formation, but several pathways to achieve a more complete inhibition of the collagen cross-linking process.
The second learning is that the next efficacy study will be conducted on recently created scars following surgery (3-12 months old).
Phase Ib Trial Design
The Phase Ib study with SNT-9465 is expected to start and be completed next year, with measures of efficacy included. It will be trialed on patients who have recently undergone open chest surgery within the last 3-12 months, creating a fairly consistent sternotomy scar across the subject pool.
Twenty patients will be recruited into the study. They will all treat themselves with the topically applied drug candidate and a placebo on different sections of the scar. Treatment will be daily for 90 days. The trial will be conducted in Western Australia and Queensland. It should be a relatively quick study. Effectively, each patient will function as their own control.
Market Opportunity & Potential Partners
CEO of Syntara Gary Phillips said the market at the moment for hypertrophic and keloid scars is estimated at $6 billion, with 45% of that market made up from sales of silicon gels and sheets, which provide minimal or short-term results.
On the topic of reimbursement, Phillips believes that the huge volume of potential patients means that an effective cream does not need to be a highly priced product in order to generate "enormous revenues". Phillips believes there may also be markets where reimbursement is relatively easy to achieve, where scars are causing functional issues. "Whether there is reimbursement or not, there will be a huge private market for this (therapy)," stated Phillips.
Phillips also believes that in the longer-term there may be a market in the cosmetics industry, citing the example of Botox, with Phillips having had discussions with the maker of that product (Allergan/AbbVie). All of the dermatology companies that Phillips has talked to are "intensely interested" in Syntara's approach to scar treatment, with this being a first-in-class drug in this field. The current study underway has been structured to answer the questions of those potential partners.
Another skin scarring study, in keloid scars (which aggressively extend beyond the wound boundary and are painful), is ongoing in Perth under Professor Fiona Wood, using the original formulation of the therapy (SNT-6302). This study is at the half-way point. Results from this study are also expected next year (1H).
Syntara had a proforma cash balance at the end of September of $14.4 million, which is expected to fund operations to the start of 2027. The company is capitalized at $52 million.
Analysis of Scarring Therapies from World Leading Scar Expert, Professor Ardeshir Bayat
Last week Syntara held an investment briefing, which featured scarring expert, plastic surgeon Professor Ardeshir Bayat, who is Director Medical Research Council of South Africa at the University of Cape Town. He is the most published and cited person in the area of keloid scarring, with over 520 publications.
Professor Bayat presented on the theme of why innovation in scarring is well overdue. Targeting LOX (that being pursued by Syntara) is one of the most compelling opportunities in this field that he has seen to date.
It is a massive unmet need and market opportunity. Each year around 100 million new scars are formed from surgery alone in the developed world, and excludes scars from accidents and C-section births. When all of these are considered, it equates to hundreds of millions of new scars each year according to Professor Bayat. "This is not a niche cosmetic condition."
Despite the need, there is still no FDA approved therapy that truly remodels scars said Professor Bayat. "Everything we have today is symptomatic, procedural or temporary."
What links all scars is what Professor Bayat describes as a downstream mechanical bottleneck, that being the collagen cross-linking. "Regardless of the cause or category, once cross-links accumulate, scars become stiff, persistent and extremely difficult to treat."
Professor Bayat said that scars are not just a cosmetic issue. Hypertrophic scars itch, burn, tighten, and restrict movement across joints. "Keloid scars are painful, disfiguring, socially stigmatizing and they tend to recur." For the patient they also cause anxiety, affect sleep, function and well-being. "That's why the willingness to try new technologies is extremely high."
"Every surgical list, every burn unit, every trauma service is effectively a scar generation engine," with burns scars requiring years of follow-up and repeated procedures. And the recurrence rates in keloid scars can approach 100% said Professor Bayat. Repeat treatment, even with lasers often makes the scars worse.
With current treatments, Professor Bayat said that we can "compress, inject, laser, cut, but we don't yet have a way to change the underlying biology of the scar."
Professor Bayat said that the unmet need is clear across doctors and patients, that being something that addresses the underlying cause that keeps scars rigid and persistent.
Professor Bayat described the current treatment as a patchwork of partial solutions. "The standard-of-care is fragmented, inconsistent and frankly outdated."
Current treatments start with silicon sheets or gels, which are not expensive, but their effect is limited or negligible. The next approach is steroids, which can flatten or soften scars, but the relapse rate is high. Lasers are expensive, operator dependent, but can help with redness or the texture of the scar. But they do not deal with the underlying biology. When all that fails surgery is an option. But with keloid scars, it often sees a larger scar return. Professor Bayat calls this "anatomic improvement without biological control."
Steroids dampen inflammation for a time. Lasers change colour and texture for a while. Surgery removes the bulk. None of these directly address the all important issue, which is collagen cross-linking.
"Across all these treatment options, there is no durable solution, with high recurrence. All of these treatments are off-label. And none of them address the underlying collagen cross-linking. That is why this field is currently stuck….we are treating the appearance of the scar, not the mechanism that keeps it rigid and persistent."
"When we treat scars, the real target is not the surface. It is indeed remodeling…we want to reduce collagen density….we want to normalize vascularity…we want to restore elasticity…we want to re-establish (extracellular) matrix turnover (to) that healthy state where collagen is continually being laid down and broken down, instead of being frozen in a rigid configuration." The aim is not a better appearance, but to achieve biological and functional correction stressed Professor Bayat.
"We are editing the façade while the structural engineering underneath is unchanged. What is missing and what does not yet exist as an approved option is a molecular therapy that targets that cross-linking, softens the extracellular matrix and re-opens the window for true re-modelling."
One of the reasons effective treatments have been slow to develop is that all scars have been treated the same, but a young hypertrophic scar is completed different to a very mature keloid scar. "This variability slows recruitment and dilutes treatment effect." And recurrence is common, if the underlying biology is not addressed. "These challenges historically blocked meaningful drug development; but they don't mean scarring is unfixable.
"And that's exactly where a LOX directed strategy combined with rigorous phenotyping (matching of similar wounds in trials) and better endpoints can finally shift the trajectory of clinical development in this area."
Another impediment to finding an effective scarring treatment has been an inability to precisely measure the biology of the scar with precision. "What has changed the field in the last five to seven years has been the arrival of modern imaging and biomechanical tools that finally allow us to quantify what matters." These include OCT (optical coherence tomography) for measuring structural vascular information, and 3D volumetric imaging for measuring scar volume with sub millimeter accuracy. And Elastography for measuring elasticity. "In short, the tools have finally caught up with the biology. We can now measure stiffness, vascularity, thickness and re-modelling with unprecedented precision."
Professor Bayat said that the design of trials also with 'split scar clinical designs' allows each patient to be their own control. This will be adopted in the forthcoming Phase Ib sternotomy trial being conducted by Syntara, where one end will be treated with the placebo, the other end with the control, and a gap in the middle with no treatment.
The LOX enzymes that Syntara is targeting is an appropriate approach, with these enzymes elevated in hypertrophic, keloid burns and post surgical scars. In Syntara's previous Phase I study with SNT-6302, a 30% reduction in collagen density was achieved. In a biological loop, Professor Bayat describes it as a stiff matrix that keeps the fibroblast cells activated which keeps stiffening the matrix, with the LOX enzymes sustaining that loop. Addressing the underlying biology also lowers the risk of scar recurrence.
"As collagen turnover resumes, microvasculature starts to re-emerge and tissue oxygenation improves." The scars then move back towards a normal phenotype rather than just some improved appearance on the surface. Professor Bayat believes that the biology in even established scars can be reversed if you "remove the mechanical lock that LOX provides."
From an investment perspective, Professor Bayat sees it as a 'white space' that presents a huge, predictable market with no approved treatments. "The market is global, steady and constantly renewing."
Professor Bayat believes that Syntara's pan LOX approach is "truly first-in-class" with proof-of-concept data already achieved showing structural reversal and vascular normalization. "LOX biology is consistent across all scar types."
Bioshares recommendation: Speculative Buy Class A
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