On March 20, 2025 Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering novel discovery of reprogramming T cell repertoire for precision immunotherapy in oncology and autoimmune diseases, reported a multi-year research collaboration in oncology and autoimmune diseases with E John Wherry, Ph.D., Director of the Institute for Immunology and Immune Health (I3H) at the University of Pennsylvania Perelman School of Medicine (Penn) (Press release, Marengo Therapeutics, MAR 20, 2025, View Source [SID1234651328]).

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The research collaboration with Dr. Wherry and his laboratory will provide deeper insights into the mechanism of action of Marengo’s selective dual T cell agonists in oncology, while also accelerating the development of its novel precision T cell depletion platform (M-STAR) through translational research investigating the use of germline TCR regions in autoimmune diseases.

"By targeting germline-encoded regions of the TCR, Marengo’s foundational platform enables the generation of new classes of selectively targeted T cell therapeutics that we believe will reprogram the T cell repertoire and unlock new therapeutic applications across a range of disease areas," said Andrew Bayliffe, Ph.D., Chief Scientific Officer of Marengo. "Partnering with the Wherry lab will improve our understanding of our selective T cell agonists in oncology and expand our pipeline of game-changing precision T cell depleters for autoimmune diseases."

Dr. Wherry, the Richard and Barbara Schiffrin President’s Distinguished Professor and chair of Systems Pharmacology and Translational Therapeutics at Penn, is a leading expert in T cell research. As demonstrated by his seminal work in characterizing mechanisms of T cell exhaustion and T cell checkpoint inhibition in oncology, Dr. Wherry’s research focuses on high-dimensional immune profiling to identify targets that harness the immune system’s ability to fight diverse immunological diseases.

"My team is dedicated to advancing innovative T cell therapies," said Professor Wherry, "The ability to selectively promote activation or depletion of T cell subsets has great potential in oncology and autoimmune diseases, respectively. Further understanding the disease association of these germline TCR regions compared to in healthy populations is relatively understudied and can identify valuable opportunities for precision immunology therapies in a range of diseases."

On March 20, 2025 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to HLX22 (AC101), an anti-HER2 monoclonal antibody, for the treatment of gastric cancer (Press release, Alligator Bioscience, MAR 20, 2025, View Source [SID1234651312]). HLX22 is being developed by Shanghai Henlius Biotech, Inc. under a sublicense from AbClon, Inc., which had previously licensed the antibody from Alligator .
The FDA’s ODD provides incentives such as tax credits for clinical trials, waiver of certain regulatory fees, and market exclusivity upon approval, supporting the continued development of HLX22 as a potential treatment for HER2-positive metastatic gastric and gastroesophageal junction (GEJ) cancer.

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Henlius is conducting a Phase 3 clinical trial (HLX22-GC-301) to evaluate HLX22/AC101 in combination with trastuzumab and chemotherapy as a first-line treatment for HER2-positive metastatic gastric and GEJ cancer. The global study is enrolling patients across the U.S., China, Japan, and Australia.

Søren Bregenholt, CEO of Alligator, commented: "The FDA’s recognition of HLX22/AC101’s potential with Orphan Drug Designation is a notable recognition. While Alligator’s is not directly involved in the development of HLX22/AC101, we continue to follow its progress as it potentially represents future income to Alligator."
Under the terms of the license agreement, Alligator is entitled to 35% of AbClon’s revenue from its sublicense agreement with Henlius.

On March 20, 2025 iOnctura, a clinical-stage biopharmaceutical company combating neglected and hard-to-treat cancers, reported it has dosed the first patient in the randomized Phase II OCULE-01 study investigating lead asset roginolisib in patients with metastatic uveal melanoma (UM), a rare cancer of the eye (Press release, iOnctura, MAR 20, 2025, View Source [SID1234651329]).

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Roginolisib is an orally dosed small molecule allosteric modulator of PI3Kδ. Allosteric modulation is a new archetype for precise inhibition of PI3Kδ, promising clinical activity without the detrimental tolerability seen with previous generations of inhibitors. In the Phase I DIONE-01 study roginolisib demonstrated an excellent safety profile and a doubling of overall survival in metastatic uveal melanoma patients compared to historical controls. With few available treatments, eye melanoma is a rapidly growing market which is projected to be worth USD 9.56B by 2032[1].

The Phase II open label, randomized, parallel-arm OCULE-01 study (NCT06717126), has been designed to assess roginolisib as a monotherapy with the primary objective to evaluate overall survival in patients. The study will have multiple sites across Europe and the US, enrolling approximately 85 patients with metastatic UM, who have progressed following at least one prior therapy.

The secondary objectives of the Phase II study will assess progression free survival, objective response rate, duration of response, time to response, disease control rate, clinical benefit rate, safety and tolerability, pharmacokinetics, safety, health care utilization and quality of life.

Late in 2024, iOnctura also received Organ Drug Designation (ODD) from the European Medicines Agency (EMA) for roginolisib. ODD provides privileged status to drugs that show promise for the treatment of rare diseases in the European Union and qualifies iOnctura for benefits including protocol assistance, market exclusivity and fee reductions. Additionally, in early 2023 the US Food and Drug Administration (FDA) granted ODD for roginolisib in UM.

Paul Nathan, Principal Investigator of the Phase II OCULE-01 study said: ‘Roginolisib has so far shown impressive tolerability and an interesting median overall survival of 16 months in patients with uveal melanoma who had progressed on prior systemic therapy. With roginolisib’s attractive safety profile and the encouraging survival data observed in the first-in-human dose study, we look forward to continuing to investigate the potential of roginolisib in patients with limited therapeutic options.’

Catherine Pickering, CEO and Co-Founder of iOnctura added: ‘We have achieved our first significant milestone for 2025 by starting one of several planned randomized Phase II studies for roginolisib. We are excited by the potential of roginolisib across a number of indications including uveal melanoma, non-small cell lung cancer and myelofibrosis, and we look forward to early data readouts by the end of the year.

On March 20, 2025 Autolus Therapeutics plc (Nasdaq: AUTL), a commercial-stage biopharmaceutical company developing, manufacturing and delivering next-generation programmed T cell therapies, reported its operational and financial results for the full year ended December 31, 2024 (Press release, Autolus, MAR 20, 2025, View Source [SID1234651313]).

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"Reflecting on 2024, it was a year of strong execution leading to significant achievements for Autolus, including our strategic deal with BioNTech and corresponding financing to bolster our balance sheet, commencing GMP operations at our in-house CAR T manufacturing facility, and finishing the year with our first FDA approval and the commercial launch of AUCATZYL," said Dr. Christian Itin, Chief Executive Officer of Autolus. "As a result, we were well positioned to attain our most important goal of bringing this transformative therapy to patients in need. Physician enthusiasm for AUCATZYL is high, demonstrated by the 33 treatment centers we now have fully authorized as of March 19, 2025. We’re encouraged by our launch progress to date."

"As we begin 2025, we have two key objectives: execute on the commercial launch of AUCATZYL in adult ALL both in the U.S. and entering new markets; and establish the next wave of investments to expand the obe-cel opportunity, advance our clinical pipeline and drive future growth. We look forward to discussing our plans to continue to expand our clinical pipeline and strategy at our R&D event in April."

Key updates and anticipated milestones:

AUCATZYL US launch
AUCATZYL was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia on November 8, 2024
AUCATZYL is the first CAR T therapy approved by the FDA with no requirement for a REMS (Risk Evaluation Mitigation Strategy) program
In December 2024, the National Comprehensive Cancer Network (NCCN) added AUCATZYL (obecabtagene autoleucel) to its Clinical Practice Guidelines in Oncology (NCCN Guidelines) for the treatment of adult patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (r/r B-ALL)
The US commercial launch progresses on track, with 33 centers authorized as of March 19, 2025 (versus the Company’s initial target of 30 by the end of Q1 2025), covering approximately 60% of the target U.S. patient population
Patient access to AUCATZYL is progressing well, with coverage secured for greater than 85% of total U.S. medical lives
Autolus continues to expect to complete authorization of 60 treatment centers by the end of 2025, covering approximately 90% of the target patient population

Obe-cel in r/r adult B-ALL – The FELIX Study and regulatory updates
In December 2024, the New England Journal of Medicine published data from the pivotal Phase 1b/2 FELIX clinical trial of obecabtagene autoleucel (obe-cel) in relapsed/refractory (r/r) adult B-cell Acute Lymphoblastic Leukemia (ALL). The data from the trial demonstrate high rates of durable responses with low incidence of greater than Grade 3 immune-related toxicity
In February 2025, the FDA published a summary of the approval of AUCATZYL on JAMA Insights, citing the product’s complete remission rate
Obe-cel is under regulatory review in both the EU and the U.K., and the Company expects to receive notification of approval status from the Medicines and Healthcare products Regulatory Agency (MHRA) and European Medicines Agency (EMA) in H2 2025
Post period, Autolus submitted obe-cel for appraisal by the U.K. National Institute for Health and Care Excellence (NICE), and a decision is expected at the time of a potential MHRA approval
Autolus has presented updated data on obe-cel in adult ALL at the Society of Hematologic Oncology (SOHO) meeting in August 2024, the Lymphoma, Leukemia & Myeloma Congress in October 2024, the American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting in December 2024, and post-period at TANDEM 2025. The data presented at these conferences builds on previously published obe-cel data, highlighting its tolerability and long-term responses. In addition, a health economic cost model has been presented, directly comparing the cost of serious adverse events across various comparable CAR-T cell therapies.
Abstracts were accepted at the European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting being held in Florence, Italy, March 30 – April 2, 2025, and the British Society for Haematology Annual Meeting in Glasgow, UK, April 27-29, 2025. The abstracts include review of data on obe-cel in adult ALL and specifically, a sub analysis of patients 55 and older.

Obe-cel in B-cell mediated autoimmune diseases
The Phase 1 dose confirmation clinical trial (CARLYSLE) in refractory systemic lupus erythematosus (SLE) patients is ongoing, with all six patients dosed. Autolus will present the initial data from this trial and development plans at its R&D event being held on April 23, 2025, and is targeting H2 2025 for the presentation of full data with longer term patient follow-up.

Early-stage pipeline programs and collaborations
Clinical programs AUTO8 and AUTO6NG are progressing, and the Company is planning updates for programs at its R&D event which will be held on April 23, 2025.
BioNTech’s product option for AUTO1/22 was not exercised as a result of BioNTech’s pipeline prioritization, and has expired as of February 8, 2025.

Q4 2024 Operational Updates:

The FDA approval for AUCATZYL triggered a $30 million milestone payment to Autolus from Blackstone in accordance with the terms of the collaboration agreement between the parties. In addition, Autolus has made a £10 million regulatory milestone payment to UCL Business Ltd. in accordance with the license agreement between the parties
The Nucleus, Autolus’ proprietary CAR T manufacturing facility designed for 2,000+ batches ​
per year​, is now licensed by the FDA and MHRA to produce commercial supply.

On March 20, 2025 Dizal (SSE: 688192), a biopharmaceutical company committed to developing novel medicines for the treatment of cancer and immunological diseases, reported new findings on golidocitinib, a first-in-class Janus kinase 1 (JAK1) only inhibitor, in combination with PD-1 antibodies for patients who have progressed on anti-PD-1 therapy (Press release, Dizal Pharma, MAR 20, 2025, View Source [SID1234651330]). The details of the trial design and clinical results will be presented at the 2025 European Lung Cancer Congress (ELCC 2025) in Paris, March 26-29.

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Recent studies showed that the dysregulated activation of the JAK/STAT pathway, which leads to the prolonged release of IFN-γ, is a significant contributor to the resistance to immune checkpoint inhibitors in cancer immunotherapy. Preclinical and clinical studies have demonstrated that the combination of JAK inhibitors with PD-1 immunotherapy can reverse or delay onset of immunotherapy resistance by modulating the JAK/STAT pathway in Hodgkin’s lymphoma and NSCLC. Golidocitinib has shown excellent clinical benefits by effectively inhibiting the JAK/STAT pathway, leading to its approval for the treatment of relapsed/refractory peripheral T-cell lymphoma (r/r PTCL) in China. Preclinical studies also show that the combination of Golidocitinib and PD-1 antibody has synergistic potentials for anti-tumor effects.

Building on these findings, an exploratory phase Ib clinical study combining golidocitinib with PD-1 antibodies was designed to explore the synergistic effects of this combined regimen in NSCLC patients who have failed from anti-PD-1 containing regimens. This study will enroll 30 locally advanced or metastatic NSCLC patients who have previously received anti-PD-1 monotherapy or anti-PD-1 therapy with platinum-containing chemotherapy regimens.

"Immunotherapy alone or with chemotherapy is commonly used as front line treatment for NSCLC patients without driver mutations. Unfortunately, resistance is inevitable and once the disease progresses, the prognosis is poor and treatment option is limited." said Xiaolin Zhang, PhD, CEO of Dizal. "The findings we are presenting at ELCC 2025 highlight the potential for Golidocitinib-based combination regimen to delay or overcome the resistance. The preliminary results are very promising and justify further clinical validation."

In addition to the golidocitinib-based combination therapy, positive results from a Phase II study of sunvozertinib in combination with Anlotinib will also be presented. Sunvozertinib combined with anlotinib was well tolerated and demonstrated encouraging antitumor activity in NSCLC patients with EGFR mutations who had failed prior EGFR-TKI therapies. As of December 25, 2024, the objective response rate (ORR) and the disease control rate (DCR) were 33.3% and 100%, respectively, in this heavily pre-treated patient population. Enrollment is ongoing and detailed results will be updated at the congress.

Dizal presentation details during ELCC 2025

Lead Author

Abstract Title

Presentation Details

Pro. Jie Hu

67P – A Phase II Study of Sunvozertinib
Combined with Anlotinib in EGFR-TKIs
Resistant EGFRm Advanced NSCLC
Patients（WU-KONG9）

Abstract #613

Poster Display Session:

Advanced NSCLC

March 28, 2025

13:00 – 13:45 CET

Pro. Hua Zhong

126TiP – An Open-Label, Single-Arm,
Phase Ib Exploratory Study to Evaluate the
Safety and Efficacy of Golidocitinib in
Combination with Anti-PD-1 in Locally
Advanced or Metastatic Non-Small Cell
Lung Cancer (NSCLC) Treated with Anti-
PD-1 Containing Regimens

Abstract #538

Poster Display Session:

Advanced NSCLC

March 28, 2025

13:00 – 13:45 CET

About golidocitinib (DZD4205)

Golidocitinib is currently the first and only Janus kinase 1 (JAK1) selective inhibitor being evaluated for the treatment of r/r PTCL. In June 2024, golidocitinib was approved by the National Medical Products Administration (NMPA) of China for the treatment of adult patients with relapsed or refractory peripheral T-cell lymphoma (r/r PTCL).

At the data cut-off date of August 31, 2023, golidocitinib has demonstrated robust and durable anti-tumor efficacy, with an ORR of 44.3%. More than 50% of the patients with tumor remission achieved a complete response with a CRR of 23.9%. Per IRC assessment, mDoR reached 20.7 months. Golidocitinib was granted Fast Track Designation by the U.S. FDA for the treatment of r/r PTCL in February 2022. In September 2023, the CDE accepted its NDA and granted Priority Review for the treatment of r/r PTCL. The Phase I clinical data of golidocitinib (JACKPOT8 PART A) was published in Annals of Oncology (Impact Factor: 51.8), and global pivotal trial data of golidocitinib for the treatment of r/r PTCL (JACKPOT PART B) was published in The Lancet Oncology (Impact Factor: 54.4).

About sunvozertinib (DZD9008)

Sunvozertinib is an irreversible EGFR inhibitor discovered by Dizal scientists targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. In August 2023, sunvozertinib received approval from NMPA to treat advanced NSCLC with EGFR exon20ins after platinum-based chemotherapies. The approval is based on the results of WU-KONG6 study, the pivotal study of sunvozertinib in platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins. In addition, sunvozertinib also demonstrated encouraging anti-tumor activity in NSCLC patients with EGFR sensitizing, T790M, and uncommon mutations (such as G719X, L861Q, etc.), as well as HER2 exon20ins.

Sunvozertinib showed a well-tolerated and manageable safety profile in the clinic. The most common drug-related TEAEs (treatment-emergent adverse event) were Grade 1/2 in nature and clinically manageable.

Two global pivotal studies are ongoing in ≥ 2nd line (WU-KONG1 Part B) and 1st line setting (WU-KONG28), respectively, in NSCLC patients with EGFR exon20ins.

Pre-clinical and clinical results of sunvozertinib were published in peer-reviewed journals Cancer Discovery and The Lancet Respiratory Medicine.