An Extension Study in Patients with Moderate to Severe Plaque Psoriasis to Evaluate the Long-term Safety, Efficacy, and Durability of Response to ESK-001

The objective of the ESK-001-018 long term extension is to evaluate the safety and efficacy of ESK-001 over time. The scientific questions it aims to answer are:
* How safe is taking ESK-001 long-term in people with moderate to severe plaque psoriasis?
* Does taking ESK-001 long-term reduce the severity of people's plaque psoriasis?
Patients will enter the long-term extension study following completion of one of the parent studies (ESK-001-016 or ESK-001-017) and will receive open-label ESK-001 twice daily for 24 weeks. After 24 weeks, the first 200 patients meeting at least PASI-75 clinical response will be randomly assigned to receive ESK-001 or placebo. At any point during this time, the patients losing the initial clinical response may return to the open-label ESK-001 treatment. Patients who complete Week 48 will return to open-label ESK-001 treatment and they will receive ESK-001 until the end of the study or discontinuation. All the remaining patients not meeting the entry criteria for the randomized withdrawal phase will continue to receive open-label ESK-001 for the remainder of the study.
Patients taking part in the study must be men or women aged at least 18 years old and have completed a previous (parent) study of ESK-001 in moderate to severe plaque psoriasis.
Patients must consent and agree to:
* ensure drug daily compliance until end of study or discontinuation.
* visit the clinic for checkups and assessments.
* provide blood and urine samples.

Start Date08 Jan 2025

Sponsor / Collaborator

Alumis, Inc.Startup

NCT06588738

/ RecruitingPhase 3

A Multicenter, Randomized, Double-Blind, Placebo and Active Comparator Controlled Phase 3 Study in Patients with Moderate to Severe Plaque Psoriasis to Evaluate the Efficacy and Safety of ESK-001 (ONWARD2)

The goal of this clinical trial is to learn if ESK-001 works to treat moderate to severe plaque psoriasis. The main questions it aims to answer are:
* Does ESK-001 reduce the severity of people's psoriasis?
* How safe is ESK-001 in people with moderate to severe plaque psoriasis?
The study includes 2 comparators: a placebo control (a 'dummy' tablet that does not contain the medicine ESK-001 but looks just like it) and an active control (apremilast, which is a medicine approved to treat psoriasis).
People taking part in this study must be men or women aged at least 18 years and have had plaque psoriasis for at least 6 months, currently moderate to severe.
Participants will:
* take drug every day for 24 weeks.
* visit the clinic for checkups and tests.
* fill out questionnaires about their psoriasis, itch severity, and change in quality of life.
* be assessed for health issues and side effects, physical examinations, vital signs, heart electrical activity measurements, and psychological health.
* provide blood and urine samples.

Start Date20 Aug 2024

Sponsor / Collaborator

Alumis, Inc.Startup

NCT06586112

/ RecruitingPhase 3

A Multicenter, Randomized, Double-Blind, Placebo and Active Comparator Controlled Phase 3 Study to Evaluate the Efficacy and Safety of ESK-001 in Patients with Moderate to Severe Plaque Psoriasis (ONWARD1)

Start Date25 Jul 2024

Sponsor / Collaborator

Alumis, Inc.Startup

100 Clinical Results associated with FTP-637

100 Translational Medicine associated with FTP-637

100 Patents (Medical) associated with FTP-637

Literatures (Medical) associated with FTP-637

01 Aug 2023·International immunopharmacology

Recent progress on tyrosine kinase 2 JH2 inhibitors

Review

Author: Liao, Tingting ; Wu, Xianbo ; Wang, Jie ; Wang, Lin ; Deng, Lidan ; Wan, Li ; Shi, Jianyou

Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family, which can regulate the signaling of multiple pro-inflammatory cytokines, including IL12, IL23 and type I interferon (IFNα/β), and its inhibitors can treat autoimmune diseases caused by the abnormal expression of IL12 and IL23. Interest in TYK2 JH2 inhibitors has increased as a result of safety concerns with JAK inhibitors. This overview introduces TYK2 JH2 inhibitors that are already on the market, including Deucravactinib (BMS-986165), as well as those currently in clinical trials, such as BMS-986202, NDI-034858, and ESK-001.

13 Apr 2023·Journal of medicinal chemistryQ1 · MEDICINE

Development and Therapeutic Implications of Tyrosine Kinase 2 Inhibitors.

Q1 · MEDICINE

Review

Author: Zhang, Xiangyu ; Wang, Tianyu ; Zhang, Kuojun ; Ye, Ke ; Qi, Zhihao ; Mao, Jie ; Jiang, Sheng ; Tang, He

Janus kinases (JAKs) are central components in cytokine signaling pathways. A number of small molecule JAK inhibitors have been approved to treat a wide range of inflammatory and autoimmune diseases. Due to safety concerns of pan-JAK inhibition, the thrust of current research is toward the discovery of isoform-selective JAK inhibitors. Selective inhibition of tyrosine kinase 2 (TYK2) has the potential to balance efficacy and safety. Substantial efforts have been made to develop selective TYK2 inhibitors: Deucravacitinib (BMS-986165) is a representative allosteric inhibitor that has been approved by the FDA, and ropsacitinib (PF-06826647) is an active site-directed inhibitor currently being evaluated in clinical trials. Herein, we outline the key roles of TYK2 in diseases, review the advances of selective TYK2 inhibitors, and finally discuss future perspectives and challenges in the development of TYK2 inhibitors.

01 Jan 2023·Journal of cutaneous medicine and surgery

Clinical Implications of Targeting the JAK-STAT Pathway in Psoriatic Disease: Emphasis on the TYK2 Pathway

Review

Author: Turchin, Irina ; Grewal, Parbeer ; Hong, Chih-Ho ; Papp, Kim A ; Loo, Wei Jing ; Gooderham, Melinda J ; Prajapati, Vimal H ; Maari, Catherine ; Vender, Ronald B ; Sauder, Maxwell

Cytokines in the interleukin (IL)−23/IL-17 axis are central to psoriasis pathogenesis. Janus kinase (JAK) signal transducer and activator of transcription (STAT) regulates intracellular signalling of several cytokines (including IL-12, 23, 22, 6, 17, and interferon (IFN)-γ) in the IL-23/IL-17 axis, and, as a result, has become a therapeutic target for psoriasis treatment. Although several JAK1-3 inhibitors, with varying degrees of selectivity, have been developed for immune-mediated inflammatory diseases, use in psoriasis is limited by a low therapeutic index as anticipated by signals from other disease indications. More selective inhibition of the JAK family is an area of interest. Specifically, selective tyrosine kinase (TYK)2 inhibition suppresses IL-23/IL-17 axis signalling, and at therapeutic doses, has a favorable safety profile compared to therapeutic doses of JAK1-3 inhibitors. Phase III efficacy and safety data for the selective allosteric TYK2-inhibitor, deucravacitinib, in adult patients with moderate-to-severe plaque psoriasis is promising. Furthermore, phase II clinical trials for ropsacitinib (PF-06826647), a selective TYK2 inhibitor, and brepocitinib (PF-06700841), a JAK1/TYK2 inhibitor, have also demonstrated efficacy and an acceptable safety profile in adult patients with moderate-to-severe plaque psoriasis. Other novel TYK2 allosteric inhibitors, NDI-034858 and ESK-001, are currently being investigated in adult patients with plaque psoriasis. This article reviews the details of the JAK-STAT pathway in psoriasis pathophysiology, the rationale for selective targeting of JAKs in the treatment of psoriasis, and provides clinical perspective on clinical trial data for JAK and TYK2 inhibitors.

News (Medical) associated with FTP-637

07 Feb 2025

·pipelinereview.com

Alumis and ACELYRIN to Merge Creating a Late-Stage Clinical Biopharma Company Dedicated to Innovating, Developing and Commercializing Transformative Therapies for Immune-mediated Diseases

Topline data from Phase 3 ONWARD trials for Alumis’ ESK-001 in moderate-to-severe plaque psoriasis on track for readout in first half of 2026; Topline data from Phase 2b LUMUS trial in systemic lupus erythematosus on track for readout in 2026 Evaluation underway of development plan for ACELYRIN’s lonigutamab to confirm differentiation in a capital efficient manner Pro forma cash position of approximately $737 million as of December 31, 2024, provides runway into 2027, beyond expected multiple clinical readouts for highly differentiated late-stage portfolio Alumis and ACELYRIN stockholders to own ~55% and ~45%, respectively, of combined company on a fully diluted basis Combined company will operate under Alumis name with current Alumis executive team SOUTH SAN FRANCISCO, CA and LOS ANGELES, CA, USA I February 06, 2025 I Alumis Inc. (Nasdaq: ALMS), a clinical-stage biopharmaceutical company developing therapies using a precision approach to optimize clinical outcomes and significantly improve the lives of patients with immune-mediated diseases, and ACELYRIN, INC. (Nasdaq: SLRN), a late-stage clinical biopharma company focused on accelerating the development and delivery of transformative medicines in immunology, today announced a definitive merger agreement under which Alumis and ACELYRIN will merge in an all-stock transaction. Martin Babler, President, Chief Executive Officer and Chairman of Alumis, said, “Through this combination with ACELYRIN, Alumis will have the financial flexibility and runway to advance an expanded late-stage pipeline, now including lonigutamab, and build commercial capabilities. Since completing our IPO, Alumis has operated with speed and rigor, and the multiple development milestones expected in 2025 and 2026, coupled with potential additional indications for ESK-001, represent exciting breakthroughs for our patients and value-driving opportunities for the combined company’s stockholders. As we move forward together, we will maintain financial discipline and a flexible capital allocation strategy with the goal of maximizing the value of our highly differentiated portfolio.” Bruce Cozadd, Chair of the ACELYRIN Board of Directors and member of the Board Transaction Committee said, “This merger represents the culmination of a thorough strategic review process by our Board and management team to determine the best and most value-maximizing path forward for ACELYRIN. We are confident that Alumis is the right partner to optimize the development of lonigutamab and together deliver long-term stockholder value.” “We are pleased to join with Alumis and further advance our mission of developing and delivering transformative medicines in immunology,” said Mina Kim, Chief Executive Officer of ACELYRIN. “This merger brings together two complementary organizations and pipelines, enabling the company to leverage the benefits of combined development and commercial expertise, as well as catalyst diversification, to achieve even more together. I am deeply grateful to the entire ACELYRIN team, whose efforts have made today’s milestone possible, and am excited that Alumis shares our mission of providing patients with life-changing new treatment options.” Alumis and ACELYRIN had cash, cash equivalents and marketable securities of approximately $289 million and approximately $448 million, respectively, on a preliminary basis, as of December 31, 2024. With a pro forma cash position of approximately $737 million as of December 31, 2024, and continued operating discipline, Alumis expects that this cash position provides runway to advance the combined company’s pipeline through multiple planned key data readouts across several clinical trials and to fund operating expenses and capital expenditure requirements into 2027. Combined Pipeline The combined company will benefit from a differentiated late-stage portfolio of therapies and increased resources enabling the development of life-changing medicines. Together, the combined company will leverage its track record of R&D success, along with its proprietary data and analytics platform, which utilizes key genetic and translational insights to optimize outcomes to patients. Alumis ACELYRIN Transaction Terms Under the terms of the agreement, ACELYRIN stockholders will receive 0.4274 shares of Alumis common stock for each share of ACELYRIN common stock owned. Upon the close of the transaction, Alumis stockholders will own approximately 55% of the combined company and ACELYRIN stockholders will own approximately 45% of the combined company, on a fully diluted basis. The transaction was unanimously recommended and approved by the disinterested directors of each company’s Board. Headquarters and Leadership Following close, the combined company will be led by the current Alumis executive team and will comprise a deep bench of talented professionals and medical experts that have successfully advanced multiple programs through clinicals trials to commercialization. This will include key members of ACELYRIN’s team who will ensure continuity and optimization of the lonigutamab development plan. The combined company’s Board will expand to nine directors, including two additional directors from ACELYRIN’s Board. The combined company will operate under the Alumis name with its corporate headquarters remaining in South San Francisco. Timing and Approvals The transaction is expected to close in the second quarter of 2025, subject to approval by the stockholders of both companies and satisfaction of other customary closing conditions. Stockholders representing approximately 62% of Alumis voting common stock and approximately 24% of ACELYRIN common stock have entered into voting agreements in support of the transaction. Conference Call and Webcast Alumis and ACELYRIN will host a joint conference call and webcast today at 5:00 p.m. E.T. to discuss the transaction. The webcast will be available live via the link here . The webcast link and associated presentation materials will be available on the investor relations section of each company’s website. Advisors Morgan Stanley & Co. LLC is serving as financial advisor to Alumis, and Cooley LLP is serving as its legal counsel. Guggenheim Securities, LLC is serving as financial advisor to ACELYRIN and Fenwick & West LLP is serving as its legal counsel. About Alumis Alumis is a clinical-stage biopharmaceutical company developing oral therapies using a precision approach to optimize clinical outcomes and significantly improve the lives of patients with immune-mediated diseases. Leveraging its proprietary precision data analytics platform, Alumis is building a pipeline of molecules with the potential to address a broad range of immune-mediated diseases as monotherapy or combination therapies. Alumis’ most advanced product candidate, ESK-001, is an oral, highly selective, small molecule, allosteric inhibitor of tyrosine kinase 2 that is currently being evaluated for the treatment of patients with moderate-to-severe plaque psoriasis and systemic lupus erythematosus. Alumis is also developing A-005, a CNS-penetrant, allosteric TYK2 inhibitor for the treatment of neuroinflammatory and neurodegenerative diseases. Beyond TYK2, Alumis’ proprietary precision data analytics platform and drug discovery expertise have led to the identification of additional preclinical programs that exemplify its precision approach. Incubated by Foresite Labs and led by a team of industry veterans experienced in small-molecule compound drug development for immune-mediated diseases, Alumis is pioneering a precision approach to drug development to potentially produce the next generation of treatment to address immune dysfunction. About ACELYRIN ACELYRIN, INC. (Nasdaq: SLRN) is focused on providing patients life-changing new treatment options by identifying, acquiring, and accelerating the development and commercialization of transformative medicines. ACELYRIN’s lead program, lonigutamab, is a subcutaneously delivered monoclonal antibody targeting IGF-1R being investigated for the treatment of thyroid eye disease. SOURCE : ACELYRIN

Phase 2Phase 3IPO

07 Feb 2025

·www.biopharmadive.com

Immune drugmakers Alumis and Acelyrin to merge

Dive Brief:Alumis and Acelyrin are merging, the biotechnology companies said Thursday afternoon, in an all-stock deal that leaves the combined company with a bigger cash balance and three drugs in clinical testing.Per deal terms, Acelryinstockholders will receive 0.4274 shares of Alumis stock for each share they own,leaving them with about 45% of the combined company and Alumis equity holders with 55%. The new company, which will keep the Alumis name and be run by its executive team, would have $737 million in cash, enough to keep operating into 2027.The merged entity will continue to develop Alumis two so-called TYK2 inhibitors, one of which is being developed for plaque psoriasis and lupus while the other is targeting neuroinflammatory conditions like multiple sclerosis. Acelyrinstop prospect, a thyroid eye disease drug called lonigutamab, is part of the deal, too, but the program will be re-evaluated to “confirm its differentiation in a capital efficient manner,“ the companies said.Dive Insight:Prior to the merger, Acelyrin and Alumis were struggling with depressed share prices. The two biotechswent public in 2023 and 2024, respectively, in large initial public offerings Acelyrin netted $540 million, while Alumis raised $250 million but both have since lost most of their market value.Acelryinhas already changed up its strategy. The company went public to support development of a drug, izokibep, being tested in multiple autoimmune conditions. But izokibep failed a late-stage study in September 2023and, a year later, was shelved in a restructuring that saw Acelyrin focus resources around lonigutamab. The company has been discussing plans to bring lonigutamabinto late-stage testing, but earlier results havent been convincing enough to lift its share price, which closed Thursday at less than $2.Alumis, meanwhile, has seen its stock sink about two thirds from its IPO price. Though the company has a TYK2 inhibitor a type of oral autoimmune medicine in late-stage testing, it trails other, similar drugs. Its development has also advanced during a crowding of competition for oral autoimmune therapies and while the only approved TYK2 blocker, Bristol Myers Squibbs Sotyktu, hasnt yet met expectations commercially.Still, Alumis has claimed its top TYK2 drug, ESK-001, could be superior to Sotyktu, and that a second candidate, A-005,has the potential to treat inflammation in the central nervous system. For ESK-001, data are expected next year from a Phase 3 trial in psoriasis and a mid-stage study in lupus. A-005 should have results from a Phase 2 test in multiple sclerosis as well.The merger, then, is a creative and capital efficient transaction that gives Alumis a significant influx of cash to get to those readouts while relieving any potential financing overhang,wrote Leerink Partners analyst Thomas Smith.The deal also enables Acelyrin shareholders to bet on those results, while handing Alumis a program in lonigutamab it could advance in parallel.We believe that scale and diversity of the portfolio is extremely important, and sufficient capital is critical, Alumis CEO Martin Babler said on a Thursday afternoon call with analysts.The drugs fate, though, is unclear. While Acelyrin has pitched it as more convenient alternativeto Amgens thyroid eye disease drug Tepezza, Wall Street analysts have been skeptical of its ability to stand out from Tepezza and a competing program from Viridian Therapeutics.Leerink analyst Smith, who connected with management following the conference call, said executives reiterated they are pausing Acelyrins previously stated plans to move lonigutamab directly into Phase 3 testing. A decision will only be made after fully assessing early study results and finding a study path that can show clear clinical differentiation, he wrote.We do not expect significant investment in lonigutamab in the near term, Smith added.The companies anticipate that the deal will close in the second quarter. '

Phase 2IPODrug ApprovalAcquisitionImmunotherapy

06 Feb 2025

·endpts.com

Less than two years after blockbuster IPO, Acelyrin merges with Alumis to combine cash, assets

After running into clinical hurdles with its “ diamond in the rough ” strategy, Los Angeles immunology biotech Acelyrin is handing over its last remaining clinical asset and $448 million in cash and equivalents in an all-stock merger with another California biotech, Alumis. Alumis will keep its name, and Alumis CEO Martin Babler and his executive team will run the combined company. It will have about $737 million in cash, based on end-of-the-year financials, and Alumis shareholders will own 55%. “Through this combination with Acelyrin, Alumis will have the financial flexibility and runway to advance an expanded late-stage pipeline, now including lonigutamab, and build commercial capabilities,” Babler said in a statement Thursday. In biotech, these types of all-stock deals can let a company that’s facing its last days transfer its equity and cash to a new company with more chances at success. Both biotechs chose to take the IPO route. Alumis went public last summer with a $250 million raise, but its shares have lost about half their value since then. Acelyrin has fared worse following its huge public offering in 2023 that raised $540 million . Soon after, its lead drug izokibep failed its first big test. The company then had a public dispute with its contract research organization about the handling of a different trial. Eventually, Acelyrin replaced its CEO last May, laid off 33% of its staff and scrapped an anti-c-Kit program in August, and then in December ended development of izokibep. Since the IPO, it has lost 89% of its value. It is still working on lonigutamab, a potential treatment for thyroid eye disease. The treatment could be a potential competitor to Amgen’s Tepezza. But a mixed Phase 2 data readout last month could make that an uphill climb. Alumis’ lead candidate is in Phase 3 for moderate-to-severe plaque psoriasis and Phase 2b for systemic lupus erythematosus. Known as ESK-001, the drug is an oral TYK2 allosteric inhibitor.

IPOPhase 3Executive ChangePhase 2Clinical Trial Failure

100 Deals associated with FTP-637

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Psoriasis of scalp	Phase 3	US	Alumis, Inc.Startup	08 Jan 2025
Plaque psoriasis	Phase 3	US	Alumis, Inc.Startup	25 Jul 2024
Plaque psoriasis	Phase 3	AU	Alumis, Inc.Startup	25 Jul 2024
Plaque psoriasis	Phase 3	CA	Alumis, Inc.Startup	25 Jul 2024
Plaque psoriasis	Phase 3	CZ	Alumis, Inc.Startup	25 Jul 2024
Plaque psoriasis	Phase 3	DE	Alumis, Inc.Startup	25 Jul 2024
Plaque psoriasis	Phase 3	PL	Alumis, Inc.Startup	25 Jul 2024
Plaque psoriasis	Phase 3	PT	Alumis, Inc.Startup	25 Jul 2024
Systemic Lupus Erythematosus	Phase 2	US	Alumis, Inc.Startup	26 Jun 2023
Systemic Lupus Erythematosus	Phase 2	AR	Alumis, Inc.Startup	26 Jun 2023

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


GlobeNewswire Manual	Phase 2	Plaque psoriasis	-	ESK-001	etveutlikd(ehfngefqmm) = ppzggiwaoz wqrttzyjtj (gfwmikhvvl ) Met View more	Positive	13 Nov 2024
NCT05600036 (STRIDE, GlobeNewswire) Manual	Phase 2	Psoriasis	-	ESK-001 40 mg twice daily (STRIDE Week 12 + NRI)	hjtzabpgou(iooyczgtxr) = ahzktrrrnh tnsabdnysh (oxhswpmchj ) View more	Positive	27 Sep 2024
				ESK-001 40 mg twice dailyESK-001 40 mg twice daily (OLE Week 28 + AO)	hjtzabpgou(iooyczgtxr) = cbtribdriw tnsabdnysh (oxhswpmchj ) View more
NCT05600036 (STRIDE, CTgov)	Phase 2	Plaque psoriasis	228	Placebo	ykxnuoiecz(zesxbceyzj) = fidtgboeja wsbsjpjamz (gmeobmuogc, lvfiemzuwi - cbamncghdo) View more	-	23 Jul 2024
NCT05739435 (GlobeNewswire) Manual	Phase 2	-	164	ESK-001 (evaluable patients)	ynzbquifpq(kvmlbylufc) = fgygqdoymx dxiudlopei (fvqaobvcrx ) View more	Positive	09 Mar 2024
				ESK-001 (non-responder imputation)	ynzbquifpq(kvmlbylufc) = egktaijyjd dxiudlopei (fvqaobvcrx ) View more
NCT05600036 (STRIDE, GlobeNewswire) Manual	Phase 2	-	228	ESK-001 10 mg QD	frstrtfsps(xoblpegxdw) = mgdfwxgpio kdiqdcnmnk (gwdcsxpepu ) Met View more	Positive	09 Mar 2024
				ESK-001 20 mg QD	frstrtfsps(xoblpegxdw) = uxvqozmggk kdiqdcnmnk (gwdcsxpepu ) Met View more

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