On May 23, 2024 IN8bio, Inc. (Nasdaq: INAB) a clinical-stage biopharmaceutical company developing innovative gamma-delta T cell therapies, reported an upcoming presentation of updated results from its fully enrolled Phase 1 study of INB-200 at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, to be held May 31st – June 4th in Chicago, Illinois (Press release, In8bio, MAY 23, 2024, View Source [SID1234643604]). INB-200 is evaluating autologous Drug Resistant Immunotherapy (DeltEx DRI) or chemotherapy resistant gamma-delta T cells as a potential first-line treatment for patients with newly diagnosed glioblastoma multiforme (GBM).

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"The current standard-of-care for newly diagnosed GBM has not advanced progression-free survival (PFS) beyond 4-7 months or overall survival beyond 14-16 months for over two decades," said William Ho, CEO and co-founder, IN8bio. "We’re excited to update the status of patients who received INB-200 for front-line GBM in addition to standard-of-care at the upcoming ASCO (Free ASCO Whitepaper) Annual Meeting. We believe these findings will continue to validate the potential of DeltEx DRI as a novel therapy for patients with GBM. We are advancing our gamma-delta T cell therapy to help address this significant unmet need and look forward to presenting additional trial results at ASCO (Free ASCO Whitepaper) and throughout the year."

Details of the 2024 ASCO (Free ASCO Whitepaper) poster presentation are provided below:

Poster title: INB-200: Fully enrolled Phase 1 study of gene-modified autologous gamma-delta (γδ) T cells in patients with newly diagnosed glioblastoma multiforme (GBM) receiving maintenance temozolomide (TMZ)
Authors: Mina Lobbous, Trishna Goswami, Lawrence Lamb, Kate Rochlin, Thriumaine Pillay, Mariska ter Haak, Louis Nabors
Date/Time: Saturday, June 1, 2024 from 10:00 a.m. – 1:00 p.m. EDT
Presenter: Dr. Mina Lobbous, University of Alabama at Birmingham
Session Title: Central Nervous System Tumors
Abstract #: 2042
Poster Board: #341

Abstract: The Phase 1 study enrolled 23 patients with newly diagnosed GBM who exhibited adequate organ function and a Karnofsky Performance Status (KPS) of ≥ 70%. Patients were administered 1, 3, or 6 doses of DeltEx DRI, consisting of 1 x 107 DRI cells, into the resection cavity along with 150 mg/m2 of intravenous TMZ on Day 1 and oral TMZ on days 2-5 of each Stupp maintenance cycle.

DeltEx DRI was successfully infused with peripheral TMZ-based lymphodepletion evidenced with near or below normal range T, B, and NK subsets for up to one year. The majority of patients dosed exceeded the expected median PFS of 7 months with Stupp therapy alone, demonstrating a continued encouraging trend in PFS. Long-term follow-up for durability of PFS and OS continue.

The Phase 1 study results reported no dose-limiting toxicities, cytokine release syndrome, or neurotoxicity. The most common adverse events were decreased white blood cell and platelet count, asthenia, fatigue, hydrocephalus, headache, decreased appetite, urinary tract infection, thrombosis, and balance disorder.

Autologous DeltEx DRI is a gene-modified autologous gamma-delta T cell therapy designed for the treatment of newly diagnosed GBM patients receiving maintenance TMZ therapy. Gamma delta T cells can target NKG2D ligands that are upregulated on tumor cells following exposure to alkylating chemotherapy, leveraging the unique capabilities of this investigational therapy to enable concomitant therapy and continued surveillance against tumor cells.

More details of the Phase 1 study can be found at www.clinicaltrials.gov (NCT04165941).

Abstract can be accessed online at View Source beginning at 5:00 p.m. EDT on May 23, 2024.

On May 23, 2024 I-Mab (the "Company") (NASDAQ: IMAB) a U.S.-based, global biotech company, exclusively focused on the development and potential commercialization of highly differentiated immunotherapies for the treatment of cancer, reported that Gerald Falchook, MD, and the team at I-Mab’s partner for ragistomig (or "ABL503"), ABL Bio (KOSDAQ: 298380), will present a poster related to Phase 1 data for ragistomig at the 2024 American Society for Clinical Oncology Annual Meeting ("ASCO 2024"), taking place from May 31st to June 4th at the McCormick Place Convention Center in Chicago, IL (Press release, I-Mab Biopharma, MAY 23, 2024, View Source [SID1234643603]).

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Ragistomig was designed as a bispecific antibody to provide anti-PD-L1 activity and 4-1BB-driven T-cell activation in one molecule. The combination of an Fc-silent and conditional 4-1BB engagement was intended to optimize the compound for safety, including the potential for lower hepatotoxicity compared to traditional 4-1BB agonists.

The first-in-human Phase 1 study was designed to define the dose-limiting toxicity and safety profile of ragistomig monotherapy (primary endpoints) as well as to observe the objective response rate (ORR), pharmacokinetic (PK) and immunogenicity profiles (secondary endpoints). The study is being conducted in patients with advanced or relapsed/refractory solid tumors and the majority of patients (56.6%) received prior anti-PD(L)-1 immunotherapy. The main observations from the study include:

· A manageable safety profile;

· Definition of an optimal dose of 5 mg/kg, with dose proportional pharmacokinetics (PK);

· Overall response rate of 25% at 5 mg/kg, based on 3 partial responses (PR) out of 12 patients with median progression free survival (PFS) of 15.6 weeks;

· Clinical benefit rate of 75% at 5 mg/kg, based on 3 PRs and 6 stable disease (SD);

· 71.4% of responders had received prior anti-PD-(L1) inhibitors and were all relapsed or refractory to anti-PD-(L1) inhibitors; and

· A complete response (CR) was seen in one heavily pretreated patient (7 prior lines of therapy, ovarian cancer) at 3 mg/kg.

"We are pleased to present the Phase 1 data to date for ragistomig at ASCO (Free ASCO Whitepaper) 2024. While immune checkpoint inhibitors have made a significant contribution to the treatment of solid tumor cancers, many tumors do not respond or become refractory to these agents. Ragistomig was designed to provide a new treatment option for patients who are resistant to immune checkpoint inhibitors," said Raj Kannan, Chief Executive Officer at I-Mab. "Topline data indicate that the study met its objectives, enabling the definition of an optimal dose, and provided several early efficacy observations in patients relapsed or refractory to prior checkpoint inhibitor treatment. These data support further development of ragistomig as both a monotherapy and in combination with other compounds. We look forward to advancing the clinical program in collaboration with our partner, ABL Bio."

Louie Naumovski, MD, PhD, Interim Chief Medical Officer for I-Mab commented, "We are pleased by ragistomig’s manageable safety, T-cell activation profile and dose proportional pharmacokinetics. Observation of responses is also encouraging, including a 25% ORR and a 75% clinical benefit rate (CBR), at the optimal dose of 5 mg/kg. Notably, the majority of patients were heavily pretreated, with three or more lines of therapy, including a prior PD-(L)1 inhibitor, and the majority of responders (71.4%) had received prior anti-PD-(L)1 therapy. Together, these data provide sound support to continue the development of ragistomig, with ongoing follow-up of this initial Phase 1 study."

The data will be reported in a poster entitled "Phase 1 trial Safety and Efficacy of Ragistomig, a Bispecific Antibody Targeting PD-L1 and 4-1BB in Advanced Solid Tumors" (Abstract #2529, Poster Board 8), at ASCO (Free ASCO Whitepaper) 2024 on June 1, 2024 from 9:00 a.m. – 12:00 p.m. C.D.T. in the Developmental Therapeutics – Immunotherapy session by Dr. Gerald Falchook, MD, Director of the Sarah Cannon Research Institute at HealthONE, a clinical trials program in Denver, Colorado, for patients with advanced cancer.

About Ragistomig

Being developed jointly with ABL Bio, ragistomig (also known as ABL503) is a differentiated PD-L1-based bispecific antibody that fuses an Fc-silent anti-PD-L1 arm, as the tumor-dependent T-cell activator, with a single chain variable fragment of an anti-4-1BB engaging antibody, as the conditional T-cell activator, upon tumor engagement. Using ABL Bio’s "Grabody-T" bispecific antibody platform technology, ragistomig/ABL503 stimulates 4-1BB activation only in the presence of PD-L1 expressing tumor cells to minimize the risk of off-tumor toxicity and overcome resistance to PD-(L)1 inhibition. Preclinical studies have demonstrated that the bispecific antibody shows better anti-tumor activity than equimolar doses of single agents alone or in combination. A Phase 1 dose escalation and dose expansion study (NCT04762641) is currently being conducted in the U.S. and South Korea. The study was designed to define the dose-limiting toxicity and adverse event profile of ragistomig (primary endpoints) as well as to observe the objective response rate, pharmacokinetic and immunogenicity profiles (secondary endpoints).

On May 23, 2024 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported positive updated results from its Phase 1/2 clinical trial of HB-200 for the treatment of human papillomavirus 16 positive (HPV16+) head and neck cancers (Press release, Hookipa Biotech, MAY 23, 2024, View Source [SID1234643601]). The data were published in the Company’s abstract for the ASCO (Free ASCO Whitepaper) 2024 Annual Meeting and support the Company’s pivotal Phase 2/3 trial design for HB-200 in combination with pembrolizumab in the first line setting.

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The abstract reported data as of January 12, 2024, and included 42 patients treated with HB-200 plus pembrolizumab. The treatment was generally well tolerated with a low rate of treatment-related discontinuation and no treatment-related deaths.

Among a subpopulation of 17 evaluable patients with CPS of 20 or higher, the updated data showed confirmed ORR of 53 percent, CR rate of 18 percent, and DCR of 82 percent. This subpopulation is representative of patients eligible for the Company’s pivotal Phase 2/3 trial, which will begin enrolling patients in the fourth quarter of 2024.

Additional data will be presented in the Head and Neck Oral Abstract Session at the ASCO (Free ASCO Whitepaper) 2024 Annual Meeting on June 4, at 11:09 a.m. CDT. During the presentation, preliminary progression-free survival and overall survival data will be shared for the first time.

"We are happy to provide an update on our clinical data and showcase the meaningful outcomes we are helping to drive for patients," said Joern Aldag, Chief Executive Officer of HOOKIPA. "The data exhibit strong evidence that has helped inform our pivotal Phase 2/3 trial design, which will begin enrolling patients later this year. This update gives us conviction that we are on the right path to achieve our goals and help provide a new targeted therapeutic option for patients battling HPV16+ head and neck cancer."

Results:
HB-200 in combination with pembrolizumab:
The abstract presented data as of January 12, 2024, and included 42 first line patients with HPV16+, PD-L1 positive, recurrent or metastatic head and neck squamous cell carcinoma. The updated data continue to demonstrate a favorable safety profile of HB-200 in combination with pembrolizumab and promising clinical activity as a first line treatment. Median follow-up time was 5.6 months.

HB-200 + pembrolizumab were generally well tolerated. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 6 (14%) patients, serious TRAEs were reported in 3 (7%) patients, and TRAEs leading to treatment discontinuation were reported in 2 (5%) patients. No treatment-related deaths were reported.

Among 35 evaluable patients—those with ≥ 1 post-baseline tumor response assessment—3 confirmed complete responses, 9 confirmed partial responses, and 3 unconfirmed partial responses were observed. Notably, among patients with PD-L1 CPS ≥20 (N=17), ORR, based on confirmed responses, was 53%, CR rate was 18%, and DCR was 82%.

Additional Abstracts at ASCO (Free ASCO Whitepaper) 2024 Annual Meeting:
HB-200 plus chemotherapy (neoadjuvant setting):
In addition, data from an Investigator Initiated Trial (IIT), led by Dr. Ari Rosenberg of the University of Chicago Department of Medicine, will be presented on June 3, in the Head and Neck Rapid Oral Abstract Session. The study concluded that neoadjuvant HB-200 plus chemotherapy for the treatment of patients with non-metastatic HPV16+ oropharyngeal cancers (OPC) is safe and feasible, with early efficacy signal in this setting warranting further study.

Twenty-one patients with HPV16+ OPC were enrolled and treated across multiple cohorts and dose levels. All patients completed neoadjuvant HB-200/chemotherapy and response-stratified locoregional treatment. Deep responses following HB-200/chemotherapy were observed in 17/21 (81%) patients, and in 14/15 (93%) patients treated with higher dose levels 1 or 2. All three patients who underwent transoral robotic surgery (TORS) had no viable tumor at time of surgery. Two patients (9%) had persistent disease following chemoradiotherapy and underwent salvage surgery with no evidence of disease at last follow-up. ctHPV-DNA and HPV16-specific T-cell response data will be presented at the meeting.

Enrollment to the subsequent randomized phase II part is ongoing. Details of the rapid oral presentation are included below.

HB-700 preclinical data:
HB-700 is an investigational arenaviral immunotherapy designed to treat KRAS-mutated lung, colorectal, pancreatic and other cancers. HB-700 is a replicating 2-vector therapy that targets the most common KRAS mutations (G12D, G12V, G12R, G12C and G13D) and has the potential to benefit a broader patient population than single mutation inhibitors.

A transgene cassette consisting of peptide stretches including KRAS mutations G12D, G12V, G12C, G12R and G13D was generated by in silico aided antigen design. KRAS mutation specific CD8+ T cell expansion was evaluated in HLA transgenic mice treated with HB-700 and functionality of induced CD8+ T cells was evaluated by assessing CD8+ T cell mediated killing of mutant KRAS peptide loaded target cells in vivo.

All treatment regimens were well tolerated, and no mortalities or major adverse events were observed. The results indicate efficient induction of KRAS mutation specific T cell responses in HLA transgenic mice. Expanded CD8+ T cells were capable of killing cells loaded with KRAS mutation specific peptides in vivo indicating functionality of the induced T cell responses. No specific cytotoxicity towards target cells pulsed with KRAS wild type peptides was observed in any of the groups. HOOKIPA’s HB-700 investigational product candidate differs from KRAS inhibitors and has a wide range of combinability options including with small-molecule inhibitors. Based on these results, initiation of a Phase I study for the treatment of KRAS mutated cancers is planned.

Abstract details: ASCO (Free ASCO Whitepaper) 2024 Annual Meeting

HB-200:
Title: HB-200 arenavirus-based immunotherapy plus pembrolizumab as first-line treatment of patients with recurrent/metastatic HPV16-positive head and neck cancer: Updated results
Presenter: Dr. Alan L. Ho, Head and Neck Oncologist at Memorial Sloan Kettering Cancer Center and a trial investigator
Abstract Type: Oral abstract
Session Name: Head and Neck Cancer
Session Date and Time: June 4, 2024; 9:45 AM-12:45 PM CDT
Abstract Number: 6005

Investigator Initiated Trial:
Title: Neoadjuvant HPV16-specific arenavirus-based immunotherapy HB-200 plus chemotherapy followed by response-stratified de-intensification in HPV16+ oropharyngeal cancer: TARGET-HPV
Presenter: Dr. Ari Rosenberg, Principal Investigator, TARGET-HPV Trial, University of Chicago Medicine
Abstract Type: Rapid oral abstract
Session Name: Head and Neck Cancer
Session Date and Time: June 3, 2024; 8:00 AM-9:30 AM CDT
Abstract Number: 6017
Trial Sponsor: UChicago Medicine

HB-700
Title: Development of an arenavirus-based immunotherapy for treatment of KRAS mutant cancer
Abstract Type: Abstract only
Session Date: May 23, 2024
Abstract Number: e14672

About HB-200
HB-200 is HOOKIPA’s lead oncology candidate engineered with the company’s proprietary replicating arenaviral vector platform. It comprises two single-vector compounds with arenaviral backbones based on lymphocytic choriomeningitis virus (LCMV) and pichinde virus (PICV). Both express the same transgene encoding an E7E6 fusion protein derived from HPV16. HB-200 is an alternating 2-vector immunotherapy designed to further focus the immune response against the encoded antigen.

HB-200 in combination with pembrolizumab received Fast Track Designation from the U.S. Food and Drug Administration and PRIME designation from the European Medicines Agency for the treatment of first-line HPV16+ recurrent/metastatic oropharyngeal squamous cell carcinoma. These designations are supported by preliminary clinical evidence from the Phase 1/2, open-label, clinical trial (NCT04180215) evaluating safety, T cell response, and efficacy based on objective response rate (ORR) and disease control rate (DCR) as defined by RECIST 1.1. and iRECIST.

About HB-700
HB-700 is an investigational arenaviral immunotherapy designed to treat KRAS-mutated lung, colorectal, pancreatic and other cancers. HB-700 is a replicating 2-vector therapy that targets the most common KRAS mutations (G12D, G12V, G12R, G12C and G13D) and has the potential to benefit a broader patient population than single mutation inhibitors.

On May 23, 2024 Heidelberg Pharma AG (FSE: HPHA), a clinical stage biotech company developing innovative Antibody Drug Conjugates (ADCs), reported that its management team will be participating and presenting on its proprietary ADC technology platforms at the following scientific conferences in May and June in 2024 (Press release, Heidelberg Pharma, MAY 23, 2024, View Source [SID1234643599]).

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Heidelberg Pharma is an ADC specialist, developing innovative drugs based on its proprietary ADC toolbox for the targeted and highly effective treatment of cancer. Its lead Amanitin-based ADC product candidate, HDP-101, targeting relapsed or refractory multiple myeloma has recently received Orphan Drug Designation (ODD) and is currently advancing in a Phase I/IIa clinical trial, demonstrating first signs of clinical efficacy. The Company is also rapidly expanding its therapeutic product pipeline with a further four programs across a variety of malignant hematologic and solid tumors.

10th Annual Oncology Innovation Forum

Date & location: 31 May 2024, Chicago, Illinois, USA

Panel: Investing in NextGen ADCs

Date: 31 May, 10:45 am CDT

Panellist: Professor Andreas Pahl, Chief Executive Officer

Presentation title: Company presentation

Date: 31 May, 02:00 pm CDT

Presenter: Professor Andreas Pahl, Chief Executive Officer

Professor Pahl will be available for one-on-one meetings, which can be arranged via the online conference system.

ASCO Annual Meeting

Date & location: 31 May–4 June 2024, Chicago, Illinois, USA

Attending: Professor Andreas Pahl, Chief Executive Officer & Dr. András Strassz, Chief Medical Officer

Professor Pahl and Dr. Strassz will be available for meetings.

BIO International Convention

Date & location: 3–6 June 2024, San Diego, California, USA

Attending: Dr. George Badescu, Chief Business Officer & Dr. Artjom Wischnjow, Associate Director Business Development

Dr. Badescu and Dr. Wischnjow will be available for one-on-one meetings, which can be arranged via the online conference system.

Jefferies Global Healthcare Conference

Date & location: 4–6 June 2024, New York, USA

Attending: Professor Andreas Pahl, Chief Executive Officer & Dr. George Badescu, Chief Business Officer

Professor Pahl and Dr. Badescu will be available for one-on-one meetings, which can be arranged via the online conference system.

On May 23, 2024 Grey Wolf Therapeutics ("Grey Wolf" or "the company"), a clinical-stage biotechnology company leveraging first-of-its-kind antigen modulation therapies to address the source of immune dysfunction in oncology and autoimmunity, reported the closing of an oversubscribed $50 million Series B financing expansion, bringing the total amount of Series B funds raised to $99 million (Press release, Grey Wolf Therapeutics, MAY 23, 2024, View Source [SID1234643598]). The Series B expansion round was led by ICG’s Life Sciences team and included further investment from existing investors Pfizer Ventures, Andera Partners, Canaan, Earlybird Venture Capital, Oxford Science Enterprises and British Patient Capital. Proceeds from the round will be leveraged to broaden the scope of the company’s ongoing Phase 1/2 clinical trial of its lead immuno-oncology candidate, GRWD5769, in a range of solid tumour types. The funding also enables the company to expand research and development (R&D) for its versatile antigen modulation approach into treatments for autoimmune disease indications.

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"The funds raised as part of this Series B expansion round allows us to enrich our ongoing clinical trial of GRWD5769 to include patients with a wider variety of tumour types and evaluate new combination treatment cohorts. In addition, the new capital enables us to more fully explore the breadth of potential therapeutic applications for our antigen modulation technology," said Peter Joyce, Ph.D., chief executive officer of Grey Wolf Therapeutics. "There is a wealth of supportive recent clinical research and compelling human genetic associations pointing to the potential for antigen modulation driven by ERAP inhibition to open the door for disease-modifying therapies in the field of autoimmune disease. As such, we are expanding our R&D efforts and evaluating these broader therapeutic applications for our unique technology."

Initial data on the ongoing adaptive Phase 1/2 trial of the lead asset GRWD5769, a first-in-class ERAP1 inhibitor will be presented at the upcoming 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting. A second ERAP1 inhibitor focussed on autoimmune disease is being advanced through IND-enabling studies with the goal of entering the clinic in 2025.

Tracy Weightman, Associate Director, Life Sciences at ICG, added, "Grey Wolf is an exciting growth stage UK biotechnology company with a novel and differentiated approach that has the potential to transform the lives of millions of patients globally. This investment demonstrates our commitment to building leading biotechnology companies and enabling them to compete on a global stage. We are pleased to support Grey Wolf through the next stage of its growth journey, enabling the company to advance its clinical development strategy and expand into new therapeutic areas."

In conjunction with the financing, Grey Wolf has announced that Ms. Weightman has been appointed to the company’s board of directors.

About ERAP Inhibition

Grey Wolf has developed and is advancing a unique therapeutic strategy that leverages the ability to effectively modulate the presentation of target antigens to the human immune system to upregulate or downregulate immune cell activity for specific therapeutic outcomes. This is achieved through the targeted inhibition of the endoplasmic reticulum aminopeptidases (ERAP1 or ERAP2), proteins that play a key role in the antigen presentation pathway. In cancer, inhibiting ERAP1 or ERAP2 drives the generation and presentation of novel and potent antigens to elicit targeted immune activity. Additionally, this mechanism works to block the production of disease-causing auto-antigens to prevent pathogenic immune responses that drive autoimmune diseases.