Adagene Announces Clinical Trial Collaboration With Merck to Advance Two Anti-CTLA-4 Monoclonal
Antibody Programs (ADG116 and ADG126) in Combination Therapy with KEYTRUDA® (pembrolizumab)

On July 22, 2021 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a platform-driven, clinical-stage biopharmaceutical company committed to transforming the discovery and development of novel antibody-based immunotherapies, reported that it has entered into the clinical trial collaboration and supply agreement with Merck (known as "MSD" outside the United States and Canada), the leader among top immuno-oncology (IO) drugs on the market (Press release, Adagene, JUL 22, 2021, View Source [SID1234585080]). The agreement includes two open-label, dose escalation and expansion clinical studies to evaluate Adagene’s anti-CTLA-4 monoclonal antibody (mAb) product candidates, ADG116 and ADG126, in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), for patients with advanced/metastatic solid tumors.

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"This collaboration with Merck and the advancement of our global clinical studies represent an important milestone in our comprehensive CTLA-4 clinical development program," said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene. "Our AI driven platforms have generated two highly differentiated CTLA-4 targeting molecules, ADG116 and ADG126. ADG116, our NEObody CTLA-4 candidate, is designed with strong antibody-dependent cellular cytotoxicity (ADCC) and softened T cell activation which combined, leading to increased potency with an improved safety profile. Our SAFEbody candidate ADG126 effectively limits on-target off-tumor toxicities in normal tissues and is designed for a superior systemic safety profile at efficacious dose levels with a significantly enhanced therapeutic window to overcome existing issues associated with current anti-CTLA-4 therapies."

Dr. Luo continued, "Although we believe that ADG116 and ADG126 have great promise as single agents, combining with KEYTRUDA may unleash the potential of dual PD-1/CTLA-4 blockade, overcoming the safety profile limitations seen historically with this combination while also modulating different T cell populations to drive new immune functions and synergies not achievable through conventional monotherapies. Our extensive preclinical and early strong clinical data support this strategy, and we look forward to combining our anti-CTLA-4 therapeutics with anti-PD-1 checkpoint inhibitors such as KEYTRUDA to fulfill the potential of this combination therapy approach. We are fortunate to have the opportunity to explore this combination with Merck and tackle two of the most potent immunotherapy targets."

"We are extremely pleased to partner with Merck to explore the therapeutic potential of ADG116 and ADG126 in combination with KEYTRUDA, as this collaboration represents an important milestone for Adagene, and for patients with advanced/metastatic solid tumors," said Steven Fischkoff, M.D., interim Chief Medical Officer of Adagene. "ADG116 program is at the 3 mg/kg dose level now which is where the commercial CTLA-4 therapy had been approved previously in mono and combination for specific indications. We expect to see differentiation going forward of our programs."

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

About CTLA-4 Clinical Development Program

ADG 116-P001: The Phase 1, open-label, dose escalation and cohort expansion study of ADG116 combined with KEYTRUDA in patients with advanced/metastatic solid tumors will be conducted at multiple sites in Asia and the United States. The study will evaluate the safety, tolerability, and recommended Phase 2 dose for ADG116 in combination with KEYTRUDA with dose escalation planned for up to 10 mg/kg. The study builds on encouraging signs of pharmacodynamic (PD) markers, favorable pharmacokinetic (PK) profile, strong early clinical data of the ADG116-1003 trial, extensive preclinical and safety tolerability data and successful Safety Review Committee meetings. In the ADG116-1003 trial, ADG116 has been well tolerated in 17 patients, with no dose-limiting toxicities or unexpected safety signals. No drug related Grade 2, Grade 3 or Grade 4 toxicities have been observed. Dosing for three additional patients has been completed in the 3 mg/kg cohort, for a total of 17 patients treated to date.

ADG 126-P001: The Phase 1, open-label, dose escalation and cohort expansion study of ADG126 combined with KEYTRUDA in patients with advanced/metastatic solid tumors will be conducted at multiple sites in Asia and the United States. It will evaluate the safety, tolerability, and recommended Phase 2 dose for ADG126 in combination with KEYTRUDA with dose escalation planed for up to 10 mg/kg. The study builds on encouraging preclinical data, demonstrating ADG126 was well tolerated at doses up to 200 mg/kg, with an encouraging antitumor response in multiple immune-competent mouse tumor models in a dose-dependent manner both as a single agent and in combination with anti-PD-1 and other therapies. In the ADG126-1001 trial, dose limiting toxicity (DLT) evaluation has been completed in six patients in the 0.1 and 0.3 mg/kg cohorts.

Evelo Biosciences to Report Second Quarter 2021 Financial Results on Thursday, July 29, 2021

On July 22, 2021 Evelo Biosciences (Nasdaq:EVLO), a clinical stage biotechnology company developing a new modality of orally delivered medicines, reported that it will host a conference call and live webcast at 8:30 a.m. ET on Thursday, July 29, 2021, to report its second quarter 2021 financial results and discuss business highlights (Press release, Evelo Biosciences, JUL 22, 2021, View Source [SID1234585079]).

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To access the live conference call, please dial 866-795-3242 (domestic) or 409-937-8909 (international) and refer to conference ID 1658301. A live webcast of the event will also be available under "News and Events" in the Investors section of Evelo’s website at View Source The archived webcast will be available on Evelo’s website approximately two hours after the completion of the event and will be available for 30 days following the call.

Cancer Research Institute Awards $28.5 Million in Grants and Fellowships

On July 22, 2021 The Cancer Research Institute (CRI), a U.S. nonprofit organization dedicated to saving more lives through the discovery and development of powerful immunotherapies for all cancers, reported that it has awarded more than $28.5 million in research grants and fellowships during the 2021 fiscal year ending June 30, 2021 (Press release, Cancer Research Institute, JUL 22, 2021, View Source [SID1234585078]). In total, CRI gave 79 awards that will support immunology and cancer immunotherapy research at 43 institutions in 8 countries.

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"Advances in immunology and cancer immunotherapy are being made at an accelerating pace thanks in part to new technologies and techniques that are opening up exciting new ways to explore the complex relationship between cancer and the immune system," said Jill O’Donnell-Tormey, Ph.D., CEO and director of scientific affairs at the Cancer Research Institute. "However, it is the brilliant scientists who apply these new tools and techniques to test their bold hypotheses that make possible true progress in the fight against cancer. CRI is proud to support their promising ideas to advance research and improve cancer patient care."

The awards, which are made possible through generous donations from individuals, foundations, and corporate sponsors who support CRI’s lifesaving mission, include:

12 Anna-Maria Kellen Clinical Accelerator Grants

These grants total $10.7 million for the launch, expansion, or ongoing support of platform studies including the AMADEUS biomarker study as well as the IPROC (ovarian cancer), PORTER (prostate cancer), and REVOLUTION (pancreatic cancer) studies testing novel immunotherapy combinations in these hard-to-treat cancers.

6 Lloyd J. Old STAR Awards

Each award provides a grant of $1.25 million over 5 years to future "stars" in the field of cancer immunology to support exploration of unconventional, high-risk/high-reward research directions that have significant potential to advance cancer immunotherapeutics. The 2021 Cancer Research Institute Lloyd J. Old STARs, or "Scientists Taking Risks" include:

Guoliang Cui, Ph.D., of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), who is studying the immunological functions of skeletal muscles and their link to T cell exhaustion in the context of cancer and chronic viral infection
Peter Edward Fecci, M.D., Ph.D., of Duke University Medical Center, who is working to understand and remove barriers to T cell function within the skull
Malay Haldar, M.D., Ph.D., of the University of Pennsylvania, who is characterizing diverse subsets of mononuclear phagocytes found within tumors and identifying pathways through which they might be targeted therapeutically
Ning Jiang, Ph.D., of the University of Pennsylvania, who is applying a systems immunology approach to characterize the T cell repertoire in cancer
Enrico Lugli, Ph.D., of the Fondazione Humanitas per la Ricerca, who is studying T cell stemness and exhaustion in immunosuppression and adoptive cell transfer immunotherapy
Ivan Zanoni, Ph.D., of Boston Children’s Hospital, who is exploring the role of the innate immune system in the development and control of colorectal cancer
31 CRI Irvington Postdoctoral Fellowships

Each fellowship provides up to $175,500 over three years to support laboratory research, training, and career development for promising young scientists working under the mentorship of leading immunologists.

3 CRI Irvington Postdoctoral Fellowships to Promote Racial Diversity

As part of CRI’s new health equity initiatives launched this year, this program is designed to address opportunity disparities in immunology and tumor immunology faced by U.S. Black, Hispanic, and Latino scientists. Each fellowship provides up to $175,500 over three years to support laboratory research, training, and career development and mentoring.

Together, the 34 fellows awarded in 2021 are working to improve our understanding of fundamental cancer and immune biology by developing new technologies like single cell-sequencing, liquid biopsies, and a personalized CAR T-on-a-chip screening platform, and by exploring topics such as antiviral immune memory, abnormal genomic elements known as retrotransposons, and natural killer cell exhaustion and re-programmability, among other promising research areas.

13 Clinic and Laboratory Integration Program (CLIP) Grants

Each grant provides $200,000 in support for the translation of basic laboratory discoveries into novel therapies that can be tested in patients. The 2021 CLIP grantees are investigating how diverse cell types like macrophages and gamma-delta T cells influence the tumor microenvironment, how the innate immune system senses and responds to threats, and how epigenetic reprogramming could boost checkpoint immunotherapy’s effectiveness.

This year, CRI is proud to announce that 5 of the 13 CLIP grantees are co-funded in partnership with the V Foundation for Cancer Research: Tullia Carmela Bruno, Ph.D., at the University of Pittsburgh; Silvio J. Gutkind, Ph.D., at the University of California, San Diego; Adilia Hormigo, M.D., Ph.D., at the Icahn School of Medicine at Mount Sinai; Justin Paul Kline, M.D., at the University of Chicago; and Tannishtha Reya, Ph.D., at the University of California, San Diego.

Additionally, Jean-Paul Wolinsky, M.D., at Northwestern University, has been named the new CRI-Chordoma Foundation CLIP Investigator, and is working to identify and target immune suppression in malignant chordoma, a rare cancer of bones of the skull base and spine.

5 Technology Impact Awards

Each award supplies seed funding of up to $200,000 to be used over 24 months to address the gap between technology development and clinical application of cancer immunotherapies. 2021 awardees are exploring research areas including T cell generation to re-establish T cell immunity, an inducible molecular memory system to overcome immunotherapy resistance, and a gene therapy platform to improve safety of drug delivery at the tumor site.

9 Impact Grants

These grants total $905,000 and include support for a glioblastoma immunotherapy consortium intended to facilitate development of novel targets for cellular therapy and a research technician pipeline program at Memorial Sloan Kettering Cancer Center aimed at attracting underrepresented minority graduate students to pursue careers in academic scientific research.

To view our full roster of 2021 grant and fellowship award recipients, visit cancerresearch.org/funding. More information about CRI’s grants, fellowships, and other programs is available at cancerresearch.org/grants.

Ribon Therapeutics Announces Publication in Cancer Cell of Pre-Clinical and Mechanism of Action Data for RBN-2397

On July 22, 2021 Ribon Therapeutics, a clinical stage biotechnology company developing therapeutics targeting stress support pathways, reported the first publication in the peer-reviewed journal, Cancer Cell, of preclinical data from its lead asset, RBN-2397, a small molecule inhibitor of PARP7 (Press release, Ribon Therapeutics, JUL 22, 2021, View Source [SID1234585077]). The published data demonstrate that inhibition of PARP7 can activate antitumor immune responses in cancer cells through restoration of Type I interferon (IFN) signaling and cause complete regressions in preclinical models. These preclinical findings support Ribon’s development program for RBN-2397 and validate targeting of PARP7, a key vulnerability in cancer stress support pathways, as a therapeutic strategy.

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PARP7 is overexpressed in a number of tumors, including squamous cell carcinoma of the lung (SCCL), which represents approximately 30% of all non-small cell lung cancers. PARP7 is the first monoPARP to be targeted therapeutically and RBN-2397 is the first potent and selective PARP7 inhibitor to enter clinical development.

"This publication in Cancer Cell demonstrates RBN-2397’s mechanism of action of inhibiting a key stress response pathway in cancer cells, illustrating how inhibition of PARP7 can elicit complete tumor regression in preclinical models, as well as tumor-specific adaptive immune response, through restoration of Type I IFN signaling in tumor cells," said Heike Keilhack, Ph.D., Senior Vice President of Biological Sciences, Ribon Therapeutics. "We are pleased that these data provide further evidence of the critical role PARP7 plays in cancer and antitumor immunity, independent of other PARPs, as well as a strong rationale for clinical development of RBN-2397."

Key findings of the publication are summarized below:

PARP7 is a monoPARP that acts as a brake in cytosolic nucleic acid sensing in a TBK1-dependent manner blocking Type I IFN signaling and antitumor immunity
RBN-2397 is a potent and selective inhibitor of PARP7, and drug effects in tumor models are dependent on PARP7, but not PARP1
Inhibition of PARP7 by RBN-2397 induces complete tumor regression in a lung cancer xenograft and tumor-specific adaptive immune memory in an immunocompetent mouse cancer model by restoration of Type I IFN signaling
"These findings illustrate the foundational science behind RBN-2397 and our preclinical programs, which we have identified by combining our deep understanding of the critical roles of NAD+-utilizing enzymes in cancer and inflammatory diseases, with our team’s drug development expertise, to bring novel treatments to patients with limited options," said Victoria Richon, Ph.D., President and Chief Executive Officer, Ribon Therapeutics. "We look forward to providing updates on our clinical studies with RBN-2397 and the rest of our pipeline leveraging our BEACON+ platform."

Ribon recently completed the dose-escalation portion of its Phase 1 trial evaluating RBN-2397 as a monotherapy in patients with advanced solid tumors. In June 2021, data from this portion of the study, presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, showed RBN-2397 was well tolerated with evidence of PARP7 inhibition and preliminary signs of antitumor activity.

The expansion portion of the Phase 1 trial is currently enrolling patients in a number of defined cohorts, including SCCL. Ribon plans to initiate a Phase 1b/2 study with checkpoint inhibitors in SCCL in the second half of 2021.

A link to the publication can be found here: View Source

About RBN-2397

RBN-2397 is an orally available small molecule inhibitor of PARP7 that Ribon Therapeutics is developing for the treatment of solid tumors. PARP7 is upregulated in response to cellular stress, including genomic instability in cancers, and acts as a brake on the cellular stress response by negatively regulating the Type I interferon response. By inhibiting PARP7 in tumor cells, RBN-2397 has been shown to directly inhibit cellular proliferation and restore interferon signaling to stimulate an innate and adaptive antitumor immune response. RBN-2397 is currently in a Phase 1 clinical trial as a monotherapy in patients with advanced solid tumors (NCT04053673). PARP7 is overexpressed in a number of tumors, including squamous cell carcinoma of the lung, or SCCL, which represents approximately 30% of all non-small cell lung cancers.

Brian McNamara appointed CEO Designate of new independent Consumer Healthcare company

On July 22, 2021 The Board of GSK (GSK) reported that Brian McNamara, the CEO of GSK Consumer Healthcare (a Joint Venture between GSK and Pfizer) has been appointed as CEO Designate of the new, listed Consumer Healthcare company which will result from the proposed demerger of Consumer Healthcare from GSK in 2022 (Press release, GlaxoSmithKline, JUL 22, 2021, https://www.gsk.com/en-gb/media/press-releases/brian-mcnamara-appointed-ceo-designate-of-new-independent-consumer-healthcare-company/ [SID1234585076]).

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As set out at GSK’s Investor Update on 23 June 2021, subject to approval from shareholders, the separation of Consumer Healthcare will be by way of a demerger in mid-2022 of at least 80% of GSK’s holding to shareholders. The new resulting Consumer Healthcare company is expected to attain a premium listing on the London Stock Exchange.

The company will be a new world-leader in Consumer Health with a portfolio which generated annual sales of more than £10 billion in 2020. The company will have a strong portfolio of brands including Sensodyne, Voltaren, Panadol and Centrum and will hold category leadership positions and major sales presences in the US and China.

Sir Jonathan Symonds, GSK Chairman, said: "We are delighted to announce Brian’s appointment to lead the proposed new Consumer Healthcare company, following a thorough process conducted by the Board. Brian is an exceptional leader, and through two global integrations, has successfully transformed GSK Consumer Healthcare into a category-leading business. His strong track record of success and deep experience of fast moving consumer goods and consumer health, proven at P&G, Novartis and GSK, means he is the right choice to unlock the potential of Consumer Healthcare as an independent company and deliver its strong prospects for sustainable sales and profit growth, high cash generation and attractive returns for shareholders."

Brian joined GSK from Novartis in 2015, where he was head of the Over the Counter (OTC) division. He has been a driving force behind two successful Joint Ventures, first between GSK and Novartis and more recently with Pfizer to create a new world-leading Consumer Healthcare business.

Brian McNamara, CEO Designate, Consumer Healthcare, said: "I am honoured to have this opportunity. Together with the many talented people we have in our business, I am looking forward to our exciting future as an independent company. I am confident we are well positioned for growth, building on our brands and innovation, with leading-edge science and human understanding, to deliver better everyday health."

Appointment and selection process

As previously communicated, the Board of GSK conducted an extensive search and selection process to appoint a CEO Designate for the new Consumer Healthcare company. The process, conducted over six months and supported by two leading global search firms, was overseen by the Nominations & Corporate Governance Committee and resulted in direct evaluation and interview of several external and internal candidates for the position.

Consumer Healthcare Board

With the separation of Consumer Healthcare, the Board of GSK has been preparing for two separate, appropriately qualified, independent boards at the point of separation. A formal process to appoint a Chair and to form a Board of Directors for the new Consumer Health company is well underway. The appointment of a Chair is expected in the second half of 2021 who will then, in accordance with best practice, lead the process of appointments to establish the new Board. This new Board will include the appropriate mix of skills, experience, diversity and continuity, relevant to Consumer Health, to represent and maximise the value of this new business for shareholders.

Notes to Editors

Brian McNamara – additional information

Brian began his career at P&G and, over a 16-year tenure, gained extensive experience in product supply, brand marketing, and customer leadership before moving to Novartis in 2004.

Brian is a Board member of the Consumer Goods Forum (CGF). He previously served as a Board Member of the Global Self Care Federation (GSCF) for seven years, acting as Chairman from February 2017 to March 2019 and, for three years was an active member of the Board of Trustees for Treloar’s – a trust providing support and independence education for young people with physical disabilities.

Brian has an undergraduate degree in Electrical Engineering from Union College in Schenectady, New York and an MBA in Finance from University of Cincinnati.