ON November 3, 2023 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, reported new data on its masked, anti-CTLA-4 SAFEbody ADG126 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting taking place in San Diego (Press release, Adagene, NOV 3, 2023, View Source [SID1234636873]). The poster presentation, Optimal Dose Selection of ADG126 (Masked Anti-CTLA-4 SAFEbody) with Significantly Widened Therapeutic Index Compared to Ipilimumab in Combination with anti-PD-1 Antibodies Informed by QSP Modeling, is available on the company’s website.

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The data, which integrate clinical results with physiologically based pharmacokinetic and quantitative systems pharmacology modeling, demonstrated that Adagene’s lead SAFEbody candidate, ADG126, is effective at targeting CTLA-4 within the tumor microenvironment (TME). This resulted in an approximately 30-fold projected pharmacokinetic difference at 10 mg/kg every three weeks (Q3W) in the TME indicating a wider therapeutic index (TI) compared to ipilimumab at 1 mg/kg Q6W, when either is combined with anti-PD-1 therapies.

The enhanced TI of ADG126 enables higher, more frequent and repeat dosing of ADG126 in combination with anti-PD-1, resulting in significantly increased CTLA-4 engagement by activated ADG126 at steady state in tumors versus circulating blood. Analyses also demonstrated that the optimal dose of ADG126 at 10 mg/kg Q3W plus pembrolizumab results in a dose-dependent efficacy profile, without a significant increase in treatment related adverse events (TRAEs).

Importantly, a clinical case example presented for the first time from an ongoing dose expansion cohort in advanced/metastatic MSS CRC* patients free of liver metastases showed that ADG126 10 mg/kg Q3W plus pembrolizumab resulted in a confirmed PR after four cycles (i.e., 12 weeks). The patient was previously treated with two lines of therapy (bevacizumab plus FOLFOX; aflibercept plus FOLFIRI) and experienced manageable Grade 3 TRAEs consistent with known adverse events from immunotherapy.

The poster concluded that initial clinical data from the SAFEbody ADG126 program support that ADG126 may provide greater clinical benefit than ipilimumab in combination with anti-PD-1 in both ‘hot’ and ‘cold’ tumors, including MSS CRC, driven by better target engagement in the TME and a favorable safety profile that enables higher, more frequent and repeat dosing.

ADG126 SAFEbody is the most advanced clinical stage anti-CTLA-4 candidate integrating masking technology and Treg depletion for superior safety and efficacy profiles. A phase 2 dose expansion cohort is ongoing to evaluate ADG126 plus pembrolizumab in patients with MSS CRC without liver metastases.

About ADG126 & SAFEbody Technology

SAFEbody technology is designed to address safety and tolerability challenges of antibody therapeutics by minimizing on-target off-tumor toxicity in healthy tissues. ADG126 is a masked anti-CTLA-4 therapy that applies the SAFEbody precision-masking technology to its parental antibody, ADG116, for conditional activation in the TME to expand the therapeutic index by addressing dose dependent toxicity issues that severely limit the dosage and dosing cycles for effective anti-CTLA-4 therapies.

Binding to the same distinct and highly conserved epitope as ADG116, the masked ADG126 is designed to provide enhanced safety and efficacy profiles due to the combination of the potent Treg depletion in the TME and partial ligand blocking by the activated ADG126, which is accumulated steadily for the prolonged tumor killing effect.

Clinical results together with detailed pharmacokinetic analyses support the unique mechanism of action for ADG126 and its profile as a potential best-in-class anti-CTLA-4 therapy.

* Microsatellite stable colorectal cancer (MSS CRC) accounts for approximately 95% of metastatic colorectal cancer patients. MSS tumors are referred to as ‘cold’ tumors, which means they don’t typically trigger a strong response from the body’s immune system. There is no currently approved immune-oncology treatment for MSS CRC.

On November 3, 2023– Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapiesfor cancer and autoimmune disease, reported new biomarker data from the TACTI-002/KEYNOTE-798 Phase II trial evaluating eftilagimod alpha ("efti"), a soluble LAG-3 protein and first-in-class MHC Class II agonist administered subcutaneously, in combination with MSD’s (Merck & Co., Inc., Rahway, NJ., USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab) as first-line treatment for patients with previously untreated unresectable or metastatic non-small cell lung cancer (NSCLC) (Press release, Immutep, NOV 3, 2023, View Source [SID1234636825]).

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The biomarker data related to blood samples from TACTI-002 patients to be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting substantiates efti’s unique immune system stimulation and can be linked to its success in first line treatment of metastatic NSCLC patients, including the positive Overall Survival results recently reported at ESMO (Free ESMO Whitepaper) Congress 2023.

Dr Frederic Triebel, Immutep CSO, said, "Immunomonitoring of blood cells is of prime importance when one would like to understand the effect of a systemic immunostimulant injected subcutaneously, like efti is. Importantly, the pharmacodynamic data from efti in combination with pembrolizumab is associated with the 35.5-month median Overall Survival in first-line treatment of metastatic non-small cell lung cancer patients expressing PD-L1 (TPS >1%) that we recently reported at ESMO (Free ESMO Whitepaper) 2023. Similar to the immune response biomarker data seen in efti’s double-blind, randomized Phase IIb trial in HER2-/HR+ metastatic breast cancer, this data further confirms efti’s unique stimulation of the immune system, which may help patients live longer."

Sustained and significant increase of interferon-gamma (IFN-γ) and C-X-C motif chemokine ligand 10 (CXCL10) serum biomarkers for systemic Th1 response were seen at three months and six months on-therapy. Among patients with a partial or complete response, 86% (6/7) showed a ≥1.4-fold change of IFN-γ and 100% (7/7) showed a ≥1.4-fold change CXCL10, after the first efti dosing.

Additionally, the early increase of absolute lymphocyte count (ALC) was significantly greater in patients that experienced a clinical benefit (e.g., overall survival, progression-free survival, complete response, partial response, stable disease), and is a potential on-treatment biomarker for response to this therapy. Furthermore, blood-based gene expression profiling (GEP) analyses revealed significant enrichment of genes involved in immune activation and cytotoxicity, including CD8 T cells, in patients with a favourable tumor response.

This biomarker data from the TACTI-002 Phase II is similar to the biomarker analysis from Immutep’s randomized, double-blind AIPAC Phase IIb trial in HER2-/HR+ metastatic breast cancer, which combined efti solely with paclitaxel chemotherapy and did not include any anti-PD-1 therapy. In that trial, the number of circulating immune cells (monocytes, activated CD8 T cells) and CXCL10 serum levels with efti increased in a statistically significant fashion compared to baseline. The increase in pharmacodynamic markers, including ALC and CD8 T Cells, were also significantly linked to improved overall survival in the efti group.

The poster titled "Biomarker results from the 1st line non-small cell lung cancer cohort of TACTI-002: pharmacodynamic effects of combining eftilagimod alpha (soluble LAG-3) and pembrolizumab" will be available on the Posters & Publications section of Immutep’s website following its presentation.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ,
USA.

About Eftilagimod Alpha (Efti)

Efti is Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity for the treatment of cancer. As a first-in-class antigen presenting cell (APC) activator, efti binds to MHC (major histocompatibility complex) Class II molecules on APC leading to activation and proliferation of CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer.

Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track Designation in 1st line HNSCC and in 1st line NSCLC from the United States Food and Drug Administration (FDA).

On November 3, 2023 Glycotope GmbH, a biotechnology company with a proprietary platform technology for developing antibodies against proteins carrying tumor-specific carbohydrate structures, reported that it will present a poster on antibodies that specifically recognize cancer-associated glycoforms of mucin-like proteins at the 2023 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Meeting, being held in San Diego, California, United States, between 1-5 November 2023 (Press release, Glycotope, NOV 3, 2023, View Source [SID1234636813]).

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Patrik Kehler, Chief Scientific Officer of Glycotope GmbH commented: "Our platform technology is suitable to target protein/carbohydrate combined epitopes with specific antibodies. We successfully generated two antibodies which target distinct, tumor-specific epitopes on two mucin-like proteins, respectively, comprising a tumor-associated glycan in combination with the specific target protein. Due to this glycan dependency, our antibodies show markedly decreased off-tumor binding which may improve safety for highly potent therapeutic approaches like ADCs, CARs or radiopharmaceutics. We are looking forward to presenting our work at the SITC (Free SITC Whitepaper) Annual Meeting 2023 and discussing our approach with leading cancer research experts."

Poster details are as follows:

Abstract: Available here

Download: Available on Nov 3, 9:00 AM PDT – here

Title: Antibodies specifically recognizing cancer-associated glycoforms of mucin-like proteins

Abstract Number: 1462

Session Date and Time: Saturday Nov 4, 2023 9:00 AM – 8:30 PM

Location: Exhibition Hall A

On November 2, 2023 Coherus BioSciences, Inc. ("Coherus", Nasdaq: CHRS) reported that senior management will participate in the following investor conferences (Press release, Coherus Biosciences, NOV 3, 2023, View Source [SID1234636750]):

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Truist Securities BioPharma Symposium In New York City on Wednesday, November 8, 2023, for 1×1 meetings only.

UBS Biopharma Conference in Miami on Thursday, November 9, 2023, a fireside chat presentation at 11:30 a.m. Eastern Time will be webcast.

6th Annual Evercore ISI HealthCONx Conference in Miami on November 28-30, 2023, a fireside chat presentation on November 30th at 12:30 p.m. Eastern Time will be webcast.

A live audio webcast and an archive of the presentations from UBS Biopharma and Evercore ISI HealthCONx conferences will be available on the investors’ page of the Coherus website at View Source

On November 2, 2023 LiliumX, an innovative BioTech start-up focused on the development of next generation antibody-based therapeutics, reported its new brand name, and welcomed three top industry leaders to the business, after securing $7.8 million in investment (Press release, Valink Therapeutics, NOV 2, 2023, View Source [SID1234637645]).

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Established in 2021 by co-founders Arne Scheu and Irsyad Khairil, following their own research into "LEGO" protein technologies when studying at the University of Oxford, LiliumX was initially founded to develop a rapid modular platform that enables the fast and efficient construction of better antibody-based drugs, such as bispecific antibody-drug conjugates (bispecific ADCs).

Following the successful demonstration of its revolutionary approach, which proved its capability to slash the time required for generation of new drug candidates from months to a single day, the advanced BioTech start-up has secured nearly $8 million in investment to drive future innovation – with the seed round led by RV Invest and supporting investors including Hoxton Ventures, SynBioVen, Metaplanet, Acequia Capital, Magnet Ventures, Oxford Angel Fund and Y Combinator (W21).

As such, the company has now rebranded to Valink Therapeutics to represent its transition from a platform-building company to a therapeutics company, and announced plans to work closely with Pharma Partners and companies developing protein-based assets alike to drive the future of antibody-based therapeutics through its modular, Universal Assembly Platform, aptly named: LiliumX.

Fundamental to this progression will be newly appointed board members and business executives, comprising of new CSO, Jose Munoz-Olaya, whose experience in preclinical bispecific antibody discovery and development across F-Star, Adaptate and Takeda strengthen Valink’s’ drug discovery pipeline, Aleksei Zeifman, Board Member of lead investor RV Invest, and new Non-Executive Director, Alexey Lugovskoy, who has over 20 years of experience in drug discovery and early development, guiding multiple oncology, autoimmunity, and fibrosis programs into the clinic. As the CEO of Diagonal, EIR at Atlas Venture, and a Dragonfly, Morphic, Merrimack and Biogen veteran, Alex boasts a proven track record in integrating biology, clinical, regulatory and business insights.

Dr Arne Scheu, co-founder and CEO of Valink Therapeutics confirmed:

"Valink Therapeutics started with a vision to find drugs that were truly novel, combining features to build and screen drug candidates that could treat cancer in synergistic and even unexpected ways. We are now excited to release a modular platform that seamlessly combines multivalency, multispecificity, and drug-conjugation, while rebranding as Valink Therapeutics to signify the extension beyond bispecificity alone, by Valency and Linking of small molecules into antibody-drug conjugates.

We are delighted to enter this next stage of development with the support of our investors, Innovate UK, and new appointments Alex Lugovskoy (NED) and Jose Munoz-Olaya (CSO)."
Aleksei Zeifman added:

"Investment in Valink Therapeutics is a great step towards realization of our vision and strategy of improving patients’ lives through innovation, where its highly differentiated technology platform enables creation and screening of new complex biological drugs, at scale. We’re very excited to see further strengthening of the team with industry veteran Alex Lugovskoy joining the Board of directors and Jose Munoz-Olaya stepping in as a CSO concomitant to the financing round. We’re looking forward to creating new drugs together with the Valink team."
A recently established VC player, RV Invest is focused on supporting highly differentiated technical solutions that can become future standards of care.

Rob Kniaz, Co-Founder of Hoxton Ventures:

"I’m thrilled with the progress of the team so far and believe this will be a truly ground-breaking innovation in getting advanced drugs to market."