On September 13, 2024 Alligator Bioscience AB and Aptevo Therapeutics reported that positive interim data from the dose escalation portion of the companies’ Phase 1 study evaluating ALG.APV-527 will be presented at a poster on Saturday, September 14, 2024, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress, taking place September 13-17, 2024, in Barcelona, ​​Spain (Press release, Alligator Bioscience, SEP 13, 2024, View Source [SID1234646560]).

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Information om presentationen
Posternummer: #668P
Titel: First-in-Human Phase I Dose Escalation Study of ALG.APV-527, a 5T4 Tumor Antigen-Conditional 4-1BB Bispecific Antibody, in Patients with Advanced Solid Tumors, Demonstrates Positive Safety, Signals of Biological Activity and Patients with Lasting Stable Disease
Presentatör: Thomas Marron, MD, PhD
Datum: Lördag, 14 september, 2024

About the study
The Phase 1 study with ALG.APV-527 is an open-label, multicenter study that will include six cohorts in a 3+3 design*. The study will be conducted in adult patients with multiple solid tumor types/histologies likely to express the 5T4 antigen, including (but not limited to) non-small cell lung cancer (NSCLC), gastric/gastroesophageal cancer, and head and neck cancer, in up to 10 clinics in the US. ALG.APV-527 will be administered intravenously every two weeks. The study will evaluate the safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of ALG.APV-527.

*In a 3+3 design, cohorts of three patients are treated with increasing dose levels. If at least two out of three or six patients suffer a so-called Dose Limiting Toxicity (DLT), the dose escalation is stopped at the current dose level.

About ALG.APV-527
ALG.APV-527 is a bispecific 4-1BB agonist, which is active only upon simultaneous binding to 4-1BB and 5T4. The molecule has the potential to be of clinical utility as 4-1BB has the ability to stimulate the immune cells (anti-tumor-specific T cells) involved in tumor fighting, making 4-1BB a particularly attractive target for cancer immunotherapy. 5T4 is a tumor-associated antigen that is expressed during fetal development but is also overexpressed on a number of solid tumors, including non-small cell lung cancer (NSCLC), breast, head and neck, cervical, renal, gastric, colon and rectal cancers.

Preclinical studies have been published in the peer-reviewed publication Molecular Cancer Therapeutics , a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). The study, which highlights the molecule’s differentiated design that minimizes systemic immune activation, while enabling highly effective tumor-specific responses, demonstrates the drug candidate’s potent activity in preclinical models.

On September 12, 2024 Immuneering Corporation (Nasdaq: IMRX), a clinical-stage oncology company seeking to develop and commercialize universal-RAS/RAF medicines for broad populations of cancer patients, reported positive initial response data from the first five patients treated with IMM-1-104 in combination with modified gemcitabine/nab-paclitaxel in first line pancreatic cancer as part of its ongoing Phase 2a clinical trial (Press release, Immuneering, SEP 12, 2024, View Source [SID1234647154]).

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"We are delighted to share today’s initial data on IMM-1-104 in combination with modified gemcitabine/nab-paclitaxel. While the initial ORR of 40% and Disease Control Rate of 80% are very encouraging – and both more than would be expected for gemcitabine/nab-paclitaxel alone- we are still in the early stages of this trial, with more scans for all five of these initial patients and for additional patients planned to come. Nevertheless, it was encouraging to see a complete response in the very first pancreatic cancer patient treated with IMM-1-104 in this combination, with the patient now on treatment for over six months," said Ben Zeskind, Ph.D., Co-Founder and CEO of Immuneering. "Looking at the bigger picture, our Phase 2a trial aims to evaluate the efficacy of IMM-1-104 in multiple settings across various tumor types, to identify the highest priority opportunities for future development. If the early trends with IMM-1-104 in combination with modified gemcitabine/nab-paclitaxel continue, we will have an exciting direction for potential future development of IMM-1-104, which could greatly improve the prognosis for a drastically underserved patient population."

Initial Results from Phase 2a Arm Evaluating IMM-1-104 with Modified Gemcitabine/nab-Paclitaxel in First Line Pancreatic Cancer as of September 12, 2024

Patient MAPK
Mutation
Variant Dose (p.o.)
Level for
IMM-1-104 %
Change
in SLD
1st Scan %
Change
in SLD
2nd Scan %
Change
in SLD
3rd Scan %
Change
in SLD
4th Scan %
Change
in SLD
5th Scan ORR/
RECIST
1 GNAS-T105Vfs*3 (*) 240mg QD -100% -100% -100% -100% next
scan CR
2 KRAS-G12V* 240mg QD -8% -10% -40% next
scan uPR°
3 KRAS-G12V* 240mg QD -4% next
scan SD
4 Unk.# 240mg QD +6% next
scan SD
5 KRAS-G12R* 240mg QD -9% next
scan eqPD**
Initial Overall Response Rate
(ORR): 40%
Initial Disease Control Rate (DCR): 80%

* Detected in plasma cfDNA or prior genomic test.
# Unknown (Unk.); MAPK pathway variant not detected in plasma cfDNA or prior genomic test.
° Partial response result classified as "unconfirmed" pending subsequent scan.
**Equivocal (eq); Patient not dosed for over two weeks during hospitalization for a preexisting condition. Scans showed ascites and a pleural effusion categorized by radiology as equivocal new lesions per RECIST 1.1. The investigator determined these to be related to the recent placement of a hepatic stent, not disease progression, and stated that the patient is improving and remains on therapy.

Source: Immuneering Corporation

To date, the first two patients in the Phase 2a arm evaluating IMM-1-104 with modified gemcitabine/nab-paclitaxel in first-line pancreatic cancer have recorded complete or partial responses for an initial response rate of 40% (2/5) and disease control rate of 80% (4/5), with the other three patients earlier in the course of treatment and all five continuing on treatment.
Benchmarks for gemcitabine/nab-paclitaxel alone in first-line pancreatic cancer patients were established by the Phase 3 MPACT study, which included 1 Complete Response (CR) out of 431 patients, a 23% Overall Response Rate, and a 48% Disease Control Rate1. Benchmarks for modified (m) Gemcitabine/nab-Paclitaxel include an 18.6% ORR2.
To date, the combination of IMM-1-104 plus modified gemcitabine/nab-paclitaxel was observed to be well tolerated, with an emerging safety profile in line with known data for both therapeutics respectively.
Based on safety data to date, the trial’s Data and Safety Monitoring Board (DSMB) has approved enrolling additional patients into this arm at 320mg QD p.o., the first of which have already been dosed and are awaiting first scans.
[1] Von Hoff, et al. N Engl J Med. 2013;369:1691-1703, [2] Ahn DH, et al. Therapeutic Advances in Medical Oncology. 2017;9(2):75-82

"These exciting early clinical findings are consistent with the preclinical data we shared at AACR (Free AACR Whitepaper) earlier this year, which pointed to synergies between IMM-1-104 and chemotherapeutics – driving deeper more durable responses than either can achieve alone," said Brett Hall, Ph.D., Chief Scientific Officer, Immuneering Corporation. "If the combination data for IMM-1-104 continues to be positive – and taking into account the excellent emerging safety profile for IMM-1-104 – one can imagine the drug’s potential inclusion in various vertical drug combinations, immune-modifying combinations, and orthogonal combinations with therapeutics with non-overlapping mechanisms of action, which Immuneering may in the future develop both on its own and in partnership with third parties."

"There is a high unmet need in pancreatic cancer for novel therapies that meaningfully improve outcomes. With current therapies in pancreatic cancer, we rarely see complete responses, and as such any treatment that leads to one is exciting and deserves further investigation, particularly when observed in the setting of a well-tolerated agent such as IMM-1-104," said Tanios Bekaii-Saab, M.D., Leader of the Gastrointestinal Cancer Disease Group for the Mayo Clinic Cancer Center enterprise wide and Medical Oncology consultant in Mayo Clinic in Phoenix, Arizona.

In the Phase 2a portion of Immuneering’s ongoing IMM-1-104 Phase 1/2a clinical trial, IMM-1-104 is being evaluated as both monotherapy and in combination with approved chemotherapeutic agents. The Phase 2a portion includes five arms, one of which focuses on patients with RAS mutant melanoma, another on patients with RAS mutant non-small cell lung cancer (NSCLC), and three arms focused on patients with pancreatic cancer. Immuneering previously announced that IMM-1-104 received fast track designation for the treatment of first- and second-line pancreatic cancer.

Near-Term Milestone Expectations

IMM-1-104

Initial data from at least one additional arm of the Phase 2a portion of the Company’s Phase 1/2a trial is expected by year end.

IMM-6-415

Initial pharmacokinetic (PK), pharmacodynamic (PD) and safety data from the Phase 1 portion of the Company’s Phase 1/2a trial is expected by year end.

Conference Call

Immuneering will host a conference call and live webcast at 4:30 p.m. ET / 1:30 p.m. PT on September 12, 2024, to discuss the results and provide a business update. Individuals interested in listening to the live conference call may do so by dialing (800) 715-9871 for U.S callers and (646) 307-1963 for other locations and reference conference ID 8890310, or from the webcast link in the "investors" section of the company’s website at www.immuneering.com A webcast replay will be available in the investor relations section on the company’s website for 90 days following the completion of the call.

About IMM-1-104

IMM-1-104 aims to achieve universal-RAS activity that selectively impacts cancer cells to a greater extent than healthy cells, through Deep Cyclic Inhibition of the MAPK pathway with once-daily dosing. IMM-1-104 is currently being evaluated in a Phase 1/2a study in patients with advanced solid tumors harboring RAS mutations (NCT05585320).

On September 12, 2024 Vironexis Biotherapeutics, focused on transforming the future of cancer treatment by pioneering AAV-delivered T-cell immunotherapy, reported the company launched from stealth, unveiling its TransJoin AAV Gene Therapy Platform and a pipeline of more than ten product candidates for blood-based cancers, solid tumor metastasis prevention, and a cancer vaccine (Press release, Vironexis Biotherapeutics, SEP 12, 2024, View Source [SID1234646797]). Vironexis’s $26 million seed financing was led by Drive Capital and Future Ventures, with participation from Moonshots Capital and Capital Factory. The company has received clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) for VNX-101, its first gene therapy product candidate, for the treatment of CD19+ acute lymphoblastic leukemia. Vironexis anticipates initiating patient enrollment of a Phase 1/2 trial of VNX-101 in the fourth quarter of 2024, which will mark the first-ever clinical trial of an AAV-delivered cancer immunotherapy. VNX-101 has received both Fast Track Designation and Rare Pediatric Disease Designation from the FDA.

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"We’re excited to launch Vironexis from stealth and reveal our noteworthy progress advancing AAV-delivered T-cell immunotherapy," said Samit Varma, co-founder and CEO of Vironexis. "Our novel technology builds on the power of T-cell immunotherapy while overcoming key shortcomings and challenges of existing approaches such as CAR-T and bispecific antibodies. We believe we have the opportunity to dramatically improve upon the safety, efficacy and durability of these drug classes, while streamlining manufacturing and significantly lessening the burden of treatment for patients. Our focus on execution has yielded an expansive pipeline and a clinic-ready lead program in just three years. We’re working as quickly as possible to transform the future of cancer treatments for patients."

TransJoin enables a patient’s body to express an engineered transgene that redirects T cells throughout the body to tumor cells. The proprietary technology requires only a single dose and provides a bridge that joins together T cells and tumor cells to promote long-term, continuous T cell-mediated tumor killing. The foundational technology for TransJoin was licensed from Nationwide Children’s Hospital. In 2022, research led by Timothy Cripe, M.D., Ph.D., Chief of the Division of Pediatric Hematology/Oncology/Bone and Marrow Transplant, describing the TransJoin technology was published in Science Advances [link here to paper]. Dr. Cripe is one of Vironexis’s co-founders, along with Mr. Varma, a seasoned biotechnology and gene therapy company entrepreneur, and Brian Kaspar, Ph.D., a notable gene therapy scientist-entrepreneur who founded AveXis, Inc. (acquired by Novartis) and pioneered the AAV gene therapy ZOLGENSMA.

"AAV is a proven delivery technology with multiple approvals since 2017. Recognizing the pivotal impact of AAV delivery for the treatment of rare diseases, we believed its unique ability to enable long-term, continuous expression of a therapeutic protein could be the missing link to overcome the myriad challenges associated with first-generation T-cell immunotherapies like CAR-T. We subsequently demonstrated the potential of this approach in the preclinical setting," said Dr. Cripe. "It’s thrilling to now be on the cusp of seeing how this technology translates in the clinical setting. Our ultimate goal is to help a vastly broader population of patients realize the tremendous benefits of T-cell immunotherapy."

Vironexis is in the process of obtaining pre-IND input from the FDA for its second program, VNX-202, as a treatment for the prevention of metastatic HER2+ cancer (including breast cancer and other tumor types), and plans to start dosing patients in a Phase 1/2 clinical trial in 2025. The company’s other current product candidates include treatments for BCMA/GPRC5D+ multiple myeloma, CD19/20+ B-cell lymphoma; treatments to prevent metastases in GD2+ neuroblastoma, HER2+ gastric cancer, PSMA+ and MSLN+ pancreatic cancer, B7H3+ ostersarcoma and GP350+ nasopharyngeal cancer; a cancer vaccine for GP350+ nasopharyngeal cancer; and a treatment for CD19+ systemic lupus erythematosus, which Vironexis plans to partner for further development.

Molly Bonakdarpour, Partner at Drive Capital commented, "As a portfolio investment, Vironexis offers an ideal blend of groundbreaking technology, impressive preclinical data, the potential for vast patient impact, and a founding team with deep, relevant expertise and a proven track record of company formation, strategic thinking, and successful execution. Vironexis’s notable productivity in a very short timeframe has been remarkable. We look forward to its upcoming transition to a clinical-stage company."

Steve Jurvetson, Co-Founder of Future Ventures, added, "We were drawn not only to the novelty of the TransJoin technology but also to its broad applicability, spanning treatments for blood-based cancers, solid tumor metastasis prevention, and cancer vaccines, as well as immune disorders. The versatility of this platform is truly standout, and the Vironexis team’s progress in rapidly building a pipeline that explores the expanse of these opportunities is extraordinary."

How TransJoin Works
Vironexis’s TransJoin technology is designed to enable the expression of a secreted T cell engager that binds the tumor cell on one side (changeable depending on the product candidate indication target) and T cells via CD3 on the other side. CD3 is a protein that helps promote T-cell recognition of and activation against cancer cells. Following a single, one-time intravenous infusion, the TransJoin technology instructs the liver to continuously secrete the bispecific protein into the bloodstream to redirect T cells to tumor cells. TransJoin provides a bridge that joins T cells and tumor cells, resulting in long-term, consistent serum levels of the therapy and, thus, long-term, consistent T-cell-mediated tumor cell killing. TransJoin’s extremely low-dose AAV delivery minimizes toxicity and adverse events.

On September 12, 2024 Oncopeptides AB, a biotech company focused on difficult-to-treat cancers, reported it has signed an exclusive license and supply agreement with SCBIO Inc., a Korean pharmaceutical company for the commercialization of Oncopeptides’ flagship drug Pepaxti in South Korea (Press release, Oncopeptides, SEP 12, 2024, View Source [SID1234646773]).

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Oncopeptides estimates the total potential deal value to be SEK 150-300 million (USD 15-30 million) until 2032 consisting of a fixed share of all sales of Pepaxti in the country, an upfront payment and several one-time payments after reaching certain milestones including the submission of a marketing authorization application and first commercial sales of Pepaxti. Should longer market exclusivity be granted, which is the ambition of the parties, market potential is larger. Based on the high unmet need of Pepaxti, Oncopeptides and SCBIO are aiming for an accelerated regulatory approval path with first sales potentially in 2026.

"Based on the strong interest among physicians, the high unmet medical need and the expanding market opportunity with a growing elderly population we believe that South Korea is an ideal steppingstone into our communicated endeavor to expand sales of Pepaxti outside EU", said Sofia Heigis, CEO of Oncopeptides. "In SCBIO, we have found a solid partner providing a good network within multiple myeloma."

Founded in 2021 and headquartered in Daejon, South Korea, SCBIO is a pharmaceutical company specialized within immune-oncology, focusing on improving wellbeing to all patients in need by smart and timely solutions for R&D, product selection, and launch strategies.

South Korea, a country with a population of just over 50 million, with both an aging population and a high average lifespan, has been identified as a good fit for Pepaxti as a maintained quality of life is particularly beneficial for elderly multiple myeloma patients. South Korea was also included in the development program of the drug and experts in the country have clinical experience from using Pepaxti.

This year, Oncopeptides has announced partnership agreements for the sale of Pepaxti on a so called named-patient basis in the Middle East and North Africa, Sub-Saharan Africa and Eurasia. The agreement with SCBIO marks the company´s first licensing agreement, where SCBIO will support Oncopeptides through multiple steps in the value chain, from regulatory approval to commercial sales. Oncopeptides continues to explore similar agreements for other markets including China and Japan.

For more information, please visit oncopeptides.com where questions and answers for investors also will be published.

On September 12, 2024 Turbine, the biological simulation company using AI to build a digital lab for predictive computational models of human cells and tissue, reported that Ono Pharmaceutical Co., Ltd. (Osaka, Japan, "Ono") has selected multiple targets identified using Turbine’s in silico Simulated Cell platform for further development (Press release, Turbine, SEP 12, 2024, View Source [SID1234646555]). Turbine will now lead in vitro validation of the identified targets in one of Ono’s priority cancer biology domains, in consultation with Ono.

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"Achieving this milestone so quickly speaks to the speed and power of our digital laboratory platform, which models foundational protein signaling logic to target disease and position therapeutic assets for clinical success," said Szabolcs Nagy, Turbine’s co-founder and Chief Executive Officer. "All within just a year, we built, trained, and tested the optimal avatars to identify targets within Ono’s priority domain, screened for all relevant perturbations, then filtered and translated millions of in silico experiments to find key hypotheses ready for validation in our wet lab. Our insights included causal factors for each target’s mechanism of action, which should simplify and speed up validation. We’re looking forward to working with our colleagues at Ono to advance this important work."

Under the terms of the collaboration, which was announced in October 2023, Turbine will receive a milestone payment for completing this phase of the research program. As Turbine leads in vitro validation studies of the selected targets in its state-of-the-art wet laboratory facilities, it will consult with Ono’s experts on plans and expected outcomes. Turbine will be eligible for additional payments related to the validation process, as well as for progress of drug development and commercialization by Ono.

"Ono is committed to innovating transformative therapies that improve outcomes for cancer patients, and identifying novel targets with robust scientific support is essential for achieving this goal," said Seishi Katsumata, Corporate Officer/Executive Director, Discovery & Research of Ono. "Turbine has provided multiple targets that have first-in-class potential, along with the biology-driven insights necessary to rapidly validate this potential. We’re excited to move these targets forward and expect that the collaboration will consequently lead to providing a new therapeutic option to cancer patients as soon as possible."