Coiled Therapeutics

Building a biotech.

Good Morning Team.

I don’t spend much time with biotechs. The vast majority fail and it can take a long time to know when failure will become inevitable.

But those which succeed can become some of the best small cap investments you can make.

And like all investments, the trick is in picking the right ones.

We’re currently tracking Solvonis, Immupharma and Incanthera. I’ve got half an eye on Poolbeg Pharma and Cizzle. Avacta, of course, is the stock that will make or break wider market sentiment when its deal comes around.

But today, I want to take a brief look at Coiled Therapeutics.

What immediately attracts me to Coiled is its strategic positioning.

It’s not a pre-clinical hopeful burning cash on animal studies with no human data to show for it. Nor is it a late-stage giant where the risk is low but the upside is already priced into a multi-billion pound market cap.

This is a clinical-stage company sitting in the sweet spot — early enough to offer serious returns but far enough along to have real, human, de-risking data in hand.

Listing on AIM as recently as March 2026 following an acquisition and £8.5 million fundraise, Coiled has assembled what could be one of the more compelling small-cap oncology investment cases in London right now.

This team has done this before.

The science is differentiated.

The data is encouraging.

And the market capitalisation, at around £40 million, leaves room for multiples of upside if the next set of clinical readouts deliver.

Origin Story

Alright, let’s do this one last time.

The company’s lead asset, AO-252, was developed by A2A Pharmaceuticals, a private US company founded in 2016 by Sridhar Vempati and a team of scientists and strategists with a background in computational chemistry and oncology drug discovery.

A2A is not a typical biotech startup - it was built around a proprietary AI and machine learning driven drug design platform called SCULPT, which uses generative AI to design new molecules to be used against structurally complex targets that traditional drug discovery approaches have largely failed to address.

The strategy at A2A has always been deliberate: develop assets to early clinical stage, demonstrate proof of concept, and then spin them out into standalone entities focused on taking those programmes through to value-creating clinical milestones.

They’ve had success with this model.

In 2018, A2A spun out its MLL-Menin inhibitor programme into a company called Biomea Fusion. Biomea completed a Nasdaq IPO in 2021, raising $153 million at a listing market capitalisation of $464 million.

Post-IPO, Biomea’s market cap peaked above $1 billion dollars.

That’s billion with a B.

The people now running Coiled Therapeutics built that value from the inside. They know what a successful execution of this model looks like, and they are attempting to replicate it.

Coiled was spun out of A2A in 2025, specifically to advance AO-252 through clinical development.

In early 2026, it completed a reverse merger with AIM-listed Roquefort Therapeutics, raised £8.5 million from institutional investors, and began trading under the ticker COIL on 27 March.

The transaction was structured so that the Coiled USA shareholders — A2A’s founders and key insiders — received the vast majority of their consideration in equity, at the same price as new investors coming in.

That alignment of interest is key because skin in the game is always a green flag. It means that the people who could have structured a deal that paid them cash took shares instead, because they believe in what’s coming.

Why TACC3 Is Exciting

Every compelling biotech investment starts with the biology. Ultimately, we’re here for multibagger returns so you need a little sex and violence.

TACC3 stands for Transforming Acidic Coiled-Coil Containing Protein 3.

Don’t worry, I’ll explain.

It’s a scaffolding protein — think of it as an organiser that coordinates multiple critical processes inside a cell, including mitosis (cell division), DNA damage repair and immune regulation.

In normal healthy adult tissue, TACC3 plays a housekeeping role.

But in cancer cells, it’s frequently overexpressed and becomes critically important to the tumour’s ability to survive, divide and evade the immune system.

The data from the Broad Institute’s DepMap project, one of the most comprehensive databases of cancer cell line dependencies ever assembled, has highlighted TACC3 as a selective target.

Cancer cells that overexpress TACC3 show strong dependency on it, meaning they struggle to survive when it’s inhibited.

But normal adult cells can manage without it.

This is the fundamental insight that makes TACC3 attractive as a drug target: it is something cancer needs and healthy adult tissue does not.

Here’s some more context. TACC3 knockout is embryonically lethal in mice — embryos cannot develop without it. But when researchers knocked out TACC3 in adult mice, the animals tolerated it without significant toxicity.

The implication for our drug development is profound because TACC3 appears to be one of those rare targets where you can hit it hard in adult patients without the collateral damage that limits so many cancer therapies.

TACC3 overexpression has been documented across a wide range of solid tumours: ovarian, breast, prostate, lung, gastric, endometrial, sarcoma and bladder cancers, among others. These are some of the most prevalent and commercially significant cancers in oncology.

The addressable patient population is massive.

One further point on TACC3 as a target: it plays a role in centrosome amplification, a phenomenon highly prevalent in aggressive tumours and associated with poor prognosis.

Centrosome amplification drives genomic instability (it accelerates the mutation and evolution of cancer cells, making them harder to treat). By targeting TACC3, AO-252 is going after one of the root causes of tumour aggressiveness, not just a downstream symptom.

What Makes AO-252 Different

AO-252 is a small molecule inhibitor — meaning it’s a conventional pill, not a biologic requiring injection.

That matters (putting patient ease aside) for commercial scalability and the breadth of settings in which it can be used.

Orally bioavailable cancer therapies command premium pricing and market penetration that injectables cannot match. Because (obviously) they’re easy to administer.

But what really sets AO-252 apart from most cancer drugs in development is the specificity of its mechanism. Rather than inhibiting TACC3 wholesale, AO-252 specifically targets the protein-protein interactions occurring at the C-terminus of TACC3.

This matters because TACC3 has two functional domains.

The C-terminus interactions are the ones that cancer cells depend on for their survival machinery. The N-terminus interactions, by contrast, are important for normal haematopoiesis — the production of healthy blood cells.

By targeting only the C-terminus, AO-252 is designed to disrupt the cancer-critical functions of TACC3 while sparing the haematopoietic role, minimising the risk of bone marrow toxicity that plagues many cancer drugs.

When AO-252 disrupts those C-terminus interactions, the downstream consequences inside a cancer cell are severe.

It inhibits multiple protein-protein interactions simultaneously, including key proteins involved in DNA damage response: DNA-PK, PARP1, BRCA, KU70, KIFC1, MBD2 and HDAC2. The net effect is the induction of severe DNA damage within the cancer cell, followed by leakage of that damaged DNA into the cytoplasm.

That DNA leakage is both a first sign of cell death and a signal. It activates the cGAS/STING innate immune pathway, one of the body’s primary mechanisms for detecting cellular damage and mounting an immune response.

STING pathway activation, in turn, stimulates dendritic cells and M1 macrophages (white blood cells if you stopped at GCSE biology) — the immune system’s frontline attackers. The result is that AO-252 doesn’t just kill cancer cells directly but also triggers your immune system to join the attack.

This dual mechanism — direct cytotoxicity plus immune activation — puts AO-252 in a hyperrare and commercially valuable category.

Most small molecule cancer drugs work through one mechanism.

The ability to engage both direct tumour killing and immune system activation in a single orally administered pill positions AO-252 as a very versatile asset, with enormous combination therapy potential.

And then there’s the blood-brain barrier.

AO-252 was specifically designed to be brain-penetrant, meaning it can cross from the bloodstream into the brain and central nervous system.

Brain metastases (cancer that has spread to the brain from a primary tumour elsewhere) represent one of the most dangerous and therapeutically underserved complications of advanced solid tumour disease.

Many otherwise effective cancer drugs cannot cross the blood-brain barrier, leaving brain metastases essentially untreatable with targeted therapies.

AO-252’s brain penetrance, confirmed in preclinical models of brain metastases, gives it an edge in a setting where patients desperately need new options.

Or often, where there are no options at all.

The breadth of preclinical activity, combined with the mechanism of action and the validated dependency of these tumour types on TACC3, paints the picture of an asset with broad therapeutic potential.

Potential being the key word at this stage.

Clinical Data

Let’s dive into the detail of what the Phase I trial has demonstrated thus far.

The trial, registered as NCT06136884, is an open-label dose escalation study being conducted in the United States in patients with advanced solid tumours whose cancer has progressed after prior treatments.

As of the April 2026 clinical update, 31 patients had been enrolled, of whom 25 were evaluable for safety and dose-limiting toxicity assessment, and 21 were evaluable for efficacy.

The median number of prior lines of therapy in this population is five.

Sadly, these are not recently diagnosed patients with many options left. They’re at the end of the road with conventional medicine - but then, that’s why clinical trial need still exists.

The dose escalation has proceeded through multiple cohorts. In the once-daily dosing cohorts, a Clinical Benefit Rate of 40% was observed — meaning 40% of patients achieved either stable disease or tumour regression. That’s a decent result in a heavily pre-treated population, but it was the transition to twice-daily dosing in Cohort 4b that produced the step-change the company was looking for.

In Cohort 4b, with twice-daily dosing delivering sustained drug exposure throughout the day, the Clinical Benefit Rate jumped to 80%.

Four out of five evaluable patients demonstrated tumour stabilisation or regression.

Treatment durations in this cohort have exceeded six months — more than double the two to three month benchmark typically achieved with salvage therapy in this patient population.

A key result: a leiomyosarcoma patient who had received nine prior lines of therapy achieved stable disease after just two cycles of AO-252.

Earlier data points from before the BID transition were already encouraging. At the time of the AIM admission in March, the company had reported tumour reductions of up to 29% in early patients at sub-therapeutic exposure levels.

By April, that had been updated to include reductions of up to 33% in endometrial cancer patients and 29% in ovarian cancer patients, again at exposure levels below what the twice-daily cohort is now achieving.

The safety profile throughout has been clean. No serious adverse events have been observed. The Maximum Tolerated Dose has not yet been reached, which means the dose escalation can continue to climb, potentially unlocking greater efficacy at higher exposure levels.

The tolerability data contrasts favourably with traditional chemotherapy and many targeted therapies, which carry significant toxicity burdens that limit dosing and quality of life.

Several additional data streams are in motion. A sub-arm of Cohort 4b is evaluating the food effect on AO-252 absorption, with data expected in late Q2 2026.

Clinical pharmacokinetic analysis has identified distinct drug exposure variances between male and female patients, which is being incorporated into refined dose modelling.

And a next-generation formulation of AO-252, designed to further improve drug exposure and duration of effect, is on track for introduction in mid-2026.

Further, a combination therapy protocol, leveraging AO-252’s immune-modulatory properties alongside immuno-oncology agents and antibody-drug conjugates, is targeted to begin in Q3.

The key question for investors is straightforward:

Does the expansion cohort data in ovarian and prostate cancer, expected in H2 2026, confirm what the dose escalation signals are suggesting?

If it does, the conversation around this asset will change quickly.

Market Opportunity

Coiled has positioned AO-252 within the precision oncology market, drawing comparisons to the drug classes that have arguably been the most commercially successful in modern oncology: PARP inhibitors, CDK4/6 inhibitors, and androgen receptor inhibitors.

Together, these drug classes address a >$20 billion market annually and have produced some of the most valuable oncology franchises in pharmaceutical history.

PARP inhibitors, led by AstraZeneca and Merck’s Lynparza and GSK’s Zejula, transformed the treatment of BRCA-mutated ovarian and breast cancers and generated billions in annual revenues.

CDK4/6 inhibitors, led by Pfizer’s Ibrance, became the standard of care in hormone receptor positive breast cancer, with Ibrance alone generating over $5 billion in annual sales at its peak.

Androgen receptor inhibitors like enzalutamide and apalutamide reshaped the treatment landscape for prostate cancer and commanded multi-billion dollar valuations.

Each of these drug classes started as a novel mechanism targeting a validated but previously undruggable pathway.

Each faced (at the time, very valid) scepticism at the clinical stage.

Each went on to become a foundational therapy in its indication.

TACC3 inhibition, with its validated target biology, broad tumour type applicability and dual mechanism of action, has the potential to become the next such class.

The near-term focus for Coiled is ovarian and prostate cancer, two indications where the clinical signals from AO-252 have been particularly encouraging and where the commercial opportunity is right there.

In ovarian cancer in particular, there remains a significant unmet need in later lines of therapy. While PARP inhibitors have improved outcomes for BRCA-mutated patients, the majority of ovarian cancer patients eventually exhaust available options and have very limited choices.

An effective, well-tolerated oral therapy with a novel mechanism and brain penetrance would address a clear gap in the treatment landscape.

In prostate cancer, the situation is similarly compelling.

Advanced prostate cancer that has become resistant to hormone therapy. Castration-resistant prostate cancer is an area of intense clinical and commercial activity.

Enzalutamide, apalutamide and darolutamide have all achieved blockbuster status.

But resistance to these agents is common, and patients who progress on them have increasingly few options.

An oral TACC3 inhibitor with a clean safety profile, demonstrating efficacy in this setting, would be entering a market actively hungry for innovation.

The M&A evidence for the commercial appetite in these indications is unambiguous.

Johnson and Johnson’s acquisition of Halda Therapeutics in November 2025 for >$3 billion — for HLD-0915, a Phase I/II oral therapy for castration-resistant prostate cancer — is the single most relevant comparable.

That’s a Phase I/II asset, in the same indication, with a similar oral small molecule profile. Coiled is at a comparable stage, in the same indication, with a market capitalisation a fraction of that size.

As a caveat, that comparison does not guarantee anything.

Every asset is different, and Halda’s drug may have had characteristics specific to its valuation. But it establishes the framework within which large pharmaceutical companies are thinking about clinical-stage prostate cancer assets, and it validates that the M&A appetite is ravenous.

Path to Partnership

One of the things that distinguishes Coiled’s strategy from many small-cap biotechs is its clarity of purpose.

The company is not trying to build a fully integrated pharmaceutical company, which usually involves horrendous dilution and many years of patience.

It’s simply trying to generate the data packages that will attract large pharmaceutical and biotechnology partners, and to enter those discussions from a position of strength.

This is a sensible and capital-efficient approach.

Fully developing a drug through Phase II and Phase III trials and bringing it to market independently requires millions of pounds and takes many years.

For a company of Coiled’s size, that path would require repeated dilutive fundraises and carry enormous execution risk.

The partnership model — licensing, co-development or outright acquisition — allows the company to crystallise significant value at a clinical inflection point, delivering returns to investors without needing to absorb the full cost and risk of late-stage development.

The data readouts expected in H2 2026 are specifically designed as partnering catalysts.

If expansion cohort data in ovarian and prostate cancer confirms the efficacy signals from dose escalation, the company will have the clinical proof of concept necessary to further develop serious discussions with major pharmaceutical companies.

The company is already engaged in discussions with large pharmaceutical companies, and the Halda transaction demonstrates that those conversations can move quickly when the data is compelling.

The existing engagement with Key Opinion Leaders in both indications is also strategically important.

KOLs — the leading academic clinicians who define the standard of care in their fields — can be decisive in pharmaceutical company acquisition decisions.

A KOL who is enthusiastic about a drug’s mechanism and early data is one of the most powerful validators an early-stage company can have. Coiled’s expanded board, with the addition of Dr Andrew Dean and his deep clinical trial expertise in ovarian and gynaecological cancers, signals that the company understands this.

The company has also been accepted into the Endless Frontier Labs programme at the NYU Stern School of Business, one of the most competitive accelerators for science and deep-tech companies globally, with only 5% of applicants graduating.

Acceptance into this programme provides access to a network of investors and industry experts and represents an independent validation of the company’s technology and commercial potential.

Better yet, there is optionality beyond AO-252.

The company’s second programme, targeting STAT-6, addresses a completely different but highly validated therapeutic area. STAT-6 is a key transcription factor in allergic and inflammatory disease (think asthma, eczema and fibrosis) - the scale of the commercial opportunity is demonstrated by Dupixent, which targets upstream IL-4/IL-13 signalling and generated over £10 billion in revenue in 2024.

Coiled’s approach uses siRNA technology to silence STAT-6 at the messenger RNA level, preventing all isoforms from forming and reducing the risk of compensatory signalling that can limit the effectiveness of small molecule inhibitors or degraders.

The new leadership team is assessing the existing STAT-6 programme for IND submission and Phase I clinical trials, which would give the company a dual-asset pipeline with presence in both oncology and immunology.

The Team

In early-stage biotech, the quality of the team is arguably the single most critical variable.

Drugs fail for various reasons, but the companies that navigate failure, adapt and create value are the ones led by people who have been through the process before.

By that standard, Coiled is unusually well resourced.

Executive Chairman Dr Sotirios Stergiopoulos served as Chief Medical Officer of Ipsen, a multi-billion dollar Euronext-listed specialty pharmaceutical company with a major oncology portfolio.

His clinical training spans Albert Einstein College of Medicine, Harvard Medical School, and the National Institutes of Health. He holds a Masters in Biotechnology Enterprise and Entrepreneurship from Johns Hopkins and is a Fellow of the Royal Society of Medicine, the American College of Physicians and the New York Academy of Medicine.

He is also a member of the American Society of Clinical Oncology and the American Association for Cancer Research. The depth and breadth of this background — spanning clinical medicine, drug development, regulatory strategy, and capital markets — is exceptional for a company of Coiled’s current size.

CEO Sridhar Vempati brings nearly two decades of experience spanning drug discovery, oncology research and business strategy.

He co-founded A2A Pharmaceuticals in 2016 and has served as its Chief Strategy Officer and Executive Vice President of Research and Development, overseeing the computational drug design platforms and pipeline that produced AO-252.

Earlier in his career he held forecasting and business development roles at Ironwood Pharmaceuticals and Rafael Pharmaceuticals, and served as an equity research analyst at Jefferies analysing biotechnology investments.

He completed a postdoctoral fellowship in leukaemia research at the Dana Farber Cancer Institute at Harvard University and holds a PhD in molecular biology from Ludwig-Maximilians-University in Germany alongside an MBA from Boston University.

CTO Chaemin Lim holds a PhD in Synthetic and Medicinal Chemistry from Seoul National University and completed postdoctoral fellowships in oncology research at the University of Pittsburgh and in medicinal chemistry at the Research Institute of Pharmaceutical Sciences at Seoul National University.

She was a founding member of A2A Pharmaceuticals and served as its Chief Scientific Officer, where she was instrumental in developing the SCULPT platform. She has overseen successful IND filings and has a proven track record advancing programmes from discovery to the clinic. In other words, she’s the architect of the technological foundation that produced AO-252.

Chief Clinical Operations Officer Robbin Frnka brings over two decades of specialised expertise in clinical research and operations in oncology and rare disease.

Her career spans Vice President of Clinical Operations at A2A Pharmaceuticals, Co-Founder of AccelSoBio, Executive Director of Clinical Development and Strategy at Proxima CRO, Head of Clinical Operations at COUR Pharma, and senior positions at Dignitana, PRA Health Sciences, the Sylvester Comprehensive Cancer Center, US Oncology and UT Southwestern Medical Center.

Clinical operations excellence — the ability to run trials efficiently, enrol patients, manage sites, and generate clean data — is one of the most underappreciated determinants of success in small biotech companies. Having someone with Frnka’s track record in this role is a significant advantage.

Collectively, this is a team that has designed drugs, filed INDs, run clinical trials, managed regulatory interactions, and navigated pharmaceutical M&A.

They are not learning on the job.

Capital Structure

At the recent placing price of 10p per share, Coiled came to market with an expected market capitalisation of approximately £42.59 million.

The fundraise raised £8.5 million gross, delivering approximately £7.7 million in net proceeds after commissions and expenses of around £800,000.

Those net proceeds are the company’s primary resource for advancing AO-252 through the expansion cohort phase and generating the H2 2026 data readouts that represent the key near-term catalysts.

The company has been explicit that this capital is designed to fund through these inflection points in 2026 and 2027.

That means investors don’t need to worry about an immediate return to the market for additional capital, provided the clinical programme proceeds as planned.

This is a risk factor to watch though, so if any delay, bear this in mind.

Looking at the significant shareholder register at admission you can see real skin in the game, as discussed above.

Vempati holds 21.46% of the enlarged share capital. Painter holds 18.70%. Stergiopoulos holds 8.55%. SOSV III LP (a supportive venture fund) holds 6.04%. A2A Pharmaceuticals holds 3.52%.

Together, the Coiled Concert Party — the insiders who built this asset — hold approximately 58% of the company’s voting rights.

These are the majority shareholders, with the vast majority of their economic interest tied to the company’s performance as a public entity. That concentration of insider ownership can be a source of liquidity risk in the near term, but it is an exceptionally strong signal of conviction in the long-term thesis.

And it also means the effective free float is tight - so share price appreciation should, in theory, be easier (as long as they hold).

Stergiopoulos and Vempati each participated in the fundraise with personal investments of £500,000. Management putting their own money in at the same price as institutional investors is the most direct possible expression of belief in what they are building.

I like it.

Milestones To Watch

The investment thesis for Coiled in 2026 is essentially a series of catalysts:

The completion of Phase I dose escalation is expected in H1 2026, accompanied by preliminary proof-of-concept safety and efficacy data from the dose escalation phase.

This will give the market the first real look at how AO-252 performs across the full dose range that has been explored, and should provide the scientific basis for expansion cohort design.

Food-effect data from the pharmacokinetic sub-arm of Cohort 4b is expected in late Q2 2026. This is a basic regulatory and formulation milestone — understanding how food affects drug absorption informs dosing instructions and can affect the drug’s commercial profile.

The next-gen formulation of AO-252 is also targeted for introduction in mid-2026. An improved formulation that enhances drug exposure could improve efficacy outcomes in the expansion cohorts relative to what has already been observed.

The combination therapy protocol study initiation is targeted for Q3 2026.

This is perhaps more significant because it begins to explore AO-252’s potential in multi-agent settings — the combination with immuno-oncology agents being the most commercially exciting possibility given the STING pathway activation data.

The 40-patient enrolment target for the expansion cohorts is also set for Q3 2026. Enrolment pace is a practical indicator of the clinical community’s enthusiasm for the trial and the feasibility of the programme timeline.

And then, in H2 2026, the comprehensive expansion cohort efficacy and safety data readouts in ovarian and prostate cancer.

These are the catalysts around which the entire near-term investment thesis is structured.

If the data confirms the 80% Clinical Benefit Rate seen in Cohort 4b, in the specific indications the company is targeting for partnering discussions, the valuation re-rating case becomes very compelling indeed.

The company has also guided that it is assessing potential to advance directly from Phase I to a registration-grade Phase II trial, which would expedite the route to market authorisation and represent an acceleration of the development timeline that the market would likely receive positively.

The Bottom Line

Strip away the complexity and the investment case for Coiled Therapeutics resolves to a relatively simple proposition.

A team with demonstrated credentials in drug development and biotech value creation, backed by a proprietary AI-driven drug design platform with a proven track record, has produced a first-in-class oral small molecule inhibitor of a validated oncology target.

That drug has shown an 80% Clinical Benefit Rate in a heavily pre-treated patient population in Phase I, with a clean safety profile, no serious adverse events and the maximum tolerated dose not yet reached.

It crosses the blood-brain barrier.

It activates the immune system as well as killing cancer cells directly.

It has shown preclinical efficacy across eight tumour types.

It is being advanced into expansion cohorts in two indications — ovarian and prostate cancer — where the M&A appetite from large pharmaceutical companies is demonstrably active, as evidenced by Johnson and Johnson’s >$3 billion acquisition of a comparable-stage asset in late 2025.

All of this sits inside a market capitalisation of approximately £40 million.

That gap is the opportunity.

For investors who understand the asset class, have sized the position appropriately for the binary risk profile, and can hold through the inevitable volatility of a small-cap AIM biotech, Coiled is one of the more interesting risk-reward propositions in London’s oncology investment landscape right now.

And you know what?

It feels good to back another company that offers a chance to the hopeless.

These investment returns aren’t purely financial.