Member Info for Krone

Since Takeda paid billions for Nimbus Therapeutics’ program in 2022, TYK2 has been one of immunology’s hottest targets.

But it’s also crowded, with biotechs herding into the signs of success and interest from big pharma. With a licensing deal announced Wednesday, Formation Bio has joined the TYK2 pack, but with a clinical strategy it believes will set it apart.

The New York-based biopharma has acquired the ex-China rights to a central nervous system-penetrant TYK2 inhibitor from Lynk Pharmaceuticals, a Hangzhou, China-based biotech, Formation exclusively told Endpoints News. Formation’s leaders say they’ve identified a lead disease in which to test the molecule, called LNK01006, that hasn’t been studied in the clinic by other TYK2 programs. Formation expects to start a Phase 1 study in early 2026 in healthy volunteers.

CEO Benjamine Liu and CBO David Steinberg said their strategy involved advancing drug candidates with well-validated targets in untested disease areas.

David Steinberg

“We’re using both AI tools, human intuition, and human expertise to identify brand-new indications where we can, in fact, be first,” Steinberg said in an interview. That helps take away “some of that competitive pressure you might face if you were second, third, fourth.”

Formation’s leaders declined to disclose the disease. It was ranked highly by both ATLAS, Formation’s internal AI-based system that ranks potential target-indication pairings by how promising they are, and by human drug experts, Liu said.

“When people look at it, it will make sense,” Steinberg said. “But you probably wouldn’t come up with it, necessarily, from first principles.”

As part of its hub-and-spoke strategy, Formation has also formed a new subsidiary called Bleecker Bio around the molecule. Lynk will receive an undisclosed upfront payment, a minority equity stake in Bleecker, and potential milestone payments of up to $605 million.

The Lynk deal is Formation’s second licensing pact since raising a $372 million Series D round in 2024, which carried a $1.7 billion valuation, according to PitchBook data. Formation previously licensed a first-in-class antibody targeting CD226.

Liu said his goal is to create a portfolio of 10 to 15 drugs over the next five years, with a mix of first- or best-in-class potential.

First reference to a potential Chief Medical Officer…

RNS 31 December 2024 - Sareum has been notified by CPF that it received notice of termination of the SRA737 licence from the US-based licensee on 26 December 2024. The notice period runs for 90 days and Sareum will meet the team from CPF to discuss what steps, if any, are appropriate to seek an alternative licensee once the asset has returned to CPF on 27th March 2025.

In the absence of any news/information to the contrary in the Half-Year and Annual Reports there must still be an evens chance that SRA737 will come good. Dr Parker would not have expended time, energy and effort in negotiating the substantially improved financial terms if he didn't believe that there is significant potential for this target. Furthermore the many references to SRA737 in recent academic papers strongly suggest that there is still life in the old dog yet! The AGM will hopefully bring much needed clarity on this.

Https://www.linkedin.com/posts/receptor-ai_drugdiscovery-cancer-ai-activity-7399458549648744448-Fufn?utm_medium=ios_app&rcm=ACoAAD9qXvEBpRADMIIum0-eEcEOeU6YAq-gGEM&utm_source=social_share_send&utm_campaign=copy_link

RNS 23 October

“ Recent additional data has confirmed that the control group were not dosed with SDC-1801, and the findings are therefore considered unrelated to SDC-1801.”

RNS dated 12 August...expected to complete within 4 months!

https://www.lse.co.uk/rns/SAR/sareum-collaboration-with-receptorai-4apkcmu0c3umkcw.html

"It's a good time for us in psoriatic practice, because of the availability of medicines with different mechanisms of action and good quality results to treat our patients,"

https://www.hcplive.com/view/deucravacitinib-zasocitinib-validate-tyk2-inhibition-psa-mease

Perhaps it will become apparent at the AGM who or what is holding up the progression of a deal…

Https://endpoints.news/keluns-trop2-adc-plus-keytruda-improves-outcomes-in-first-line-lung-cancer/?u=7263f1cc-73d0-4481-b5b5-34aab3aee6bd&s=email&c=79153abc-746f230b-e0ab068a&utm_medium=email&utm_campaign=2338%20-%20Kelun%20scores%20lung%20cancer%20win%20with%20ADC%20JJs%20Alzheimer%20candidate%20fails%20study%20Basic&utm_content=2338%20-%20Kelun%20scores%20lung%20cancer%20win%20with%20ADC%20JJs%20Alzheimer%20candidate%20fails%20study%20Basic+CID_83d0dc698b3b3bf2ad0b7d1f38e0fe93&utm_source=ENDPOINTS%20emails&utm_term=Keluns%20TROP2%20ADC%20plus%20Keytruda%20improved%20outcomes%20in%20lung%20cancer%20study

Ex-AI

Rationale for the combination

1. Mechanism of SRA737:

• SRA737 inhibits CHK1, a key checkpoint kinase that helps tumor cells survive DNA damage and replication stress.

• By inhibiting CHK1, tumor cells may accumulate more DNA damage, become more genomically unstable, and thus potentially become more immunogenic (greater neo-antigen burden, increased immune infiltration) or more vulnerable to immune attack.

• From the company’s website: “preclinical data demonstrates synergy of SRA737 … in combinations with immune checkpoint …” 

2. Mechanism of Keytruda:

• Keytruda targets PD-1 on T-cells, blocking the PD-1/PD-L1 interaction and thereby reinvigorating T-cell immune responses. 

• Immune checkpoint inhibitors are frequently combined with therapies that increase tumor antigenicity (e.g., chemotherapy, radiation, DDR inhibitors) because the more “visible” or stressed the tumor is, the more likely immune checkpoint blockade may succeed.

3. Preclinical evidence of synergy:

• For example: a 2019 news note: SRA737 + low-dose gemcitabine (LDG) plus anti-PD-L1 immunotherapy produced “durable tumour regression” in a small‐cell lung cancer model (in mice) — 10/10 tumour regressions at end of 21-day treatment, 8/10 sustained complete response after further 39 days. 

• Also, in review literature around CHK1 inhibitors and immunotherapy, it is noted that combinations of chemotherapy/DDR inhibitors + immune checkpoint inhibitors are an emerging strategy. 

• From the corporate presentation: “Clinical safety data supports use of SRA737 in combination with other anti-cancer agents – e.g. lung cancer: Immunotherapy combinations…” 

Thus, mechanistically, combining SRA737 (which increases tumour stress / damage) with Keytruda (which unleashes immune attack) makes scientific sense.

https://www.fiercepharma.com/pharma/fda-grants-game-changing-perioperative-approval-padcev-keytruda-combo-bladder-cancer?utm_medium=email&utm_source=nl&utm_campaign=LS-NL-FierceBiotech+Tracker&oly_enc_id=8331F3744801G2C

Sareum Holdings is entering a highly promising phase, with increasing momentum across its pipeline and growing industry interest in its next-generation TYK2/JAK1 and CHK1 inhibitor programmes. The company’s strengthened IP position underpins long-term value and provides important strategic flexibility as discussions around the future development of SRA737 continue to advance. Recent sector activity suggests an encouraging environment for high-quality assets, and Sareum’s progress places it well for potential near-term catalysts.

With a newly appointed joint corporate broker expected to help raise the company’s market profile and broaden investor reach, Sareum is well positioned to benefit from expanding awareness of its differentiated science. The company maintains a disciplined development strategy, robust scientific foundations, and exposure to major growth markets in oncology and autoimmune disease—offering new investors an attractive opportunity at a compelling inflection point.

Interesting to consider Roivant's most recent results in the context of the often repeated references by Sareum to the effect that SDC-1801 is significantly superior to Brepocitinib! (Plenty of material for a bit of flag waving!)

Recent References by Sareum to Brepocitinib:

1. Full-Year Results (FY Ended 30 June 2024)

- Sareum compares SDC-1801 to brepocitinib.

- Phase 1 (MAD) study: SDC-1801 reached plasma exposures similar to 100 mg QD brepocitinib, without the serum creatinine and reticulocyte/neutrophil changes associated with brepocitinib.

- Notes renal side effect of brepocitinib (creatinine increase) linked to OCT2 inhibition; claims greater selectivity vs OCT2 for SDC-1801.

2. Spotlight / Update Document (Nov 2024)

- Positions SDC-1801 close mechanistically to brepocitinib (both TYK2/JAK1 dual inhibitors).

- Highlights longer SDC-1801 half-life (17–20h) vs brepocitinib (~6–8h).

- Notes brepocitinib shows strong efficacy, but cross-study comparisons are directional due to trial differences.

3. Interim Results / HY 2025 Presentation

- Again compares SDC-1801 to brepocitinib: exposure approx. equivalent to 100 mg QD brepocitinib.

- SDC-1801 showed no hematology or creatinine changes, unlike brepocitinib.

4. Edison / Analyst Commentary

- Edison notes Sareum uses brepocitinib as a benchmark for SDC-1801.

- Highlights Sareum’s emphasis on potential safety advantage over brepocitinib.

Analysis & Interpretation

- Strategic positioning: brepocitinib used as key comparative benchmark.

- Safety differentiation: SDC-1801 avoids creatinine and hematologic changes seen with brepocitinib.

- Exposure comparisons: Achieves similar exposure to brepocitinib without adverse effects.

- Longer half-life may provide meaningful clinical differentiation.

https://investor.roivant.com/news-releases/news-release-details/roivant-reports-financial-results-second-quarter-ended-1

The wife?

Not forgetting the potential for orphan status in hard to treat or underserved patient populations.

The original article to which this 11th November British Journal of Pharmacology 'letter to the editor refers' has previously been flagged on here.

The letter further suggests current interest in the potential application for SRA737 iJAK1–STAT3 activation and cardiac remodelling, which presumably further enhances the attractiveness of SRA737 as a target with multiple potential applications. The clock is surely winding down on news in respect of SRA737.

"We read with considerable interest the recent study by Xu and colleagues in the British Journal of Pharmacology, which reports that phosphorylation of checkpoint kinase 1 (CHK1) at serine-280 links angiotensin II (Ang II) to Janus kinase 1 (JAK1)–signal transducer and activator of transcription 3 (STAT3) activation and maladaptive cardiac remodelling in murine cardiomyocytes (Xu et al., 2025). The authors also show that inhibition of CHK1 with CCT245737 or that of JAK1 with upadacitinib limited hypertrophy, fibrosis and functional decline, even without lowering blood pressure. For the pharmacology community, this is a particularly notable finding because it places Ang II signalling in the heart, firmly beyond its haemodynamic effects. Our intention here is not to restate their conclusions, but rather to consider how these results could be validated and translated further.

https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.70259?campaign=wolearlyview

Or….

Sareum Holdings plc is pleased to report a highly successful presence at BIO-Europe Vienna, where COO Dr Tim Mitchell held a series of productive meetings with prospective partners, investors and sector specialists. Discussions highlighted strong and growing interest in Sareum’s differentiated TYK2 programmes, including early data supporting the potential for blood–brain barrier penetration in selected assets. Engagement was also positive around the company’s CHK1 candidate SRA737 and its emerging role within next-generation DDR strategies. The company believes the momentum generated in Vienna further strengthens opportunities for value-adding collaborations and supports the next phase of Sareum’s development.

Something along these lines perhaps?

Sareum COO Engages at BIO-Europe Vienna

Sareum Holdings plc reports a highly positive presence at BIO-Europe Vienna, where COO Dr Tim Mitchell met with prospective partners and investors. Strong interest was received in Sareum’s oncology pipeline, including SRA737, with discussions highlighting fresh collaboration opportunities and growing industry momentum behind the company’s development strategy.

SUDO-550, an oral TYK2 inhibitor being developed by Sudo Biosciences, was found to be safe, well-tolerated, and to fully reach the brain in a first-in-human clinical trial involving healthy volunteers, according to clinical trial results. The Phase 1 clinical trial, which began dosing late last year, also showed signs of near-complete inhibition of SUDO-550’s target in the blood and in the brain.

https://multiplesclerosisnewstoday.com/news-posts/2025/11/05/experimental-ms-therapy-safely-reaches-brain-first-human-trial/

As recently as 23rd October Dr Parker stated:

"In parallel, we secured the licence to SRA737 on substantially improved terms, and we are actively assessing the most effective routes to progress and create value from this asset....With these foundations in place, we enter the new financial year with confidence and a clear set of milestones ahead."

Furthermore the IMC slide notes:

SRA737: Clinical-stage oncology asset with broad combination potential

• Selective Chk1 inhibitor targeting cancer cell replication stress and DNA damage

repair pathways.

• Two Phase 1/2 trials completed, funded by Sierra Oncology, showing good

tolerability as monotherapy and in combination with chemotherapy.

• Sareum now has control of the programme and increased economic interest

(63.5%, up from 27.5%).

• Clinical safety data supports use of SRA737 in combination with other anti-cancer

agents – e.g.

• Lung cancer: Immunotherapy combinations induced tumour regression and durable

response in preclinical studies.

• Ovarian cancer: Restored PARP inhibitor sensitivity in resistant models, synergy with

WEE1 inhibitors

• Open IND with US FDA and sufficient drug product to conduct the planned trial in

AML and MDS patients.

• Reviewing future options: evaluating re-licensing, partnering, or internal

development to maximise asset value.

One has to ask why, if SRA737 is in fact dead in the water, would Dr P be spending what appears to be a considerable amount of time, effort and resouce creating a clear sense that the target still has value? In the absence of news on SDC-1801 until mid-2026 at best, there's not a lot else to generate shareholder value. SDC-1802 and the as yet unnamed neuroscience asset have the potential to create a flurry of interest however SRS737 is well done the development path and as such has the greatest near term promise. If it turns out that the BoD have been less than direct there will justifiably be some very uncomfortable questions to answer. I prefer to think that Dr Parker is indeed working diligently to create shareholder value in the near term.

Dr Stephen Parker, Executive Chairman of Sareum, said: "We believe SRA737 remains a valuable asset, and gaining control of the licence puts us in a stronger position to explore potential partnerships or development opportunities. Given the existing clinical data, we remain optimistic about identifying a path forward that maximises SRA737's value."