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 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 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 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 Neogap Therapeutics AB, a Swedish biotechnology company developing personalised immunotherapy for cancer treatment, reported that initial safety data from the first patients in its ongoing phase I/II trial corroborates that the treatment is well tolerated (Press release, Neogap Therapeutics, MAR 20, 2025, View Source [SID1234651314]). No serious treatment-related adverse events have been observed, reinforcing confidence in the therapy’s safety profile.

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"Safety data from the first two treated patients confirm that Neogap’s immunotherapy is well tolerated and further strengthen our confidence in its potential as a valuable treatment option for patients with difficult-to-treat cancer. The trial is progressing as planned, and we continue to gather data to assess the safety profile and analyse clinical outcomes and biomarkers as part of the exploratory evaluation," says Samuel Svensson, CEO of Neogap Therapeutics.

The ongoing phase I/II trial is a first-in-human study designed to assess the safety and tolerability of Neogap’s personalised immunotherapy, pTTL (personalised Tumour Trained Lymphocytes), in patients with advanced colorectal cancer. Several patients have already been enrolled, with the first having completed treatment. Recruitment and treatment of additional patients continue. In total, 12–16 patients are planned to receive treatment. The study is being conducted at several hospitals in Sweden, including Karolinska University Hospital, Västmanland Hospital, and Danderyd Hospital.

About Neogap’s immunotherapy, pTTL
pTTL (personalised Tumour Trained Lymphocytes) is a cell-based immunotherapy that enhances the patient’s own T cells to fight cancer. The therapy combines advanced DNA analysis with T-cell expansion in a precision treatment for solid tumours. It is based on Neogap’s patented technologies, PIOR and EpiTCer. The goal is to provide patients with a tailored and innovative therapy that meets their specific needs.