On December 6, 2021 GRAIL, LLC, a healthcare company whose mission is to detect cancer early when it can be cured, reported a partnership with Alignment Health Plan, a national Medicare Advantage health plan from Alignment Healthcare (NASDAQ: ALHC), to provide its Medicare Advantage members access to Galleri, GRAIL’s groundbreaking multi-cancer early detection blood test (Press release, Grail, DEC 6, 2021, View Source [SID1234596509]). Based in Orange, California, Alignment Health Plan is the first Medicare Advantage plan to offer the Galleri test as a complement to recommended single cancer screenings.

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"Providing innovative benefits to support the health and care needs of our members is what we do here at Alignment," said Dawn Maroney, markets president, Alignment Healthcare, and CEO, Alignment Health Plan (CA). "Taking preventive measures before signs and symptoms appear is key to finding cancer early when it is most treatable. We are excited to partner with GRAIL to provide seniors the tools they need to proactively manage their health."

New and existing Alignment Health Plan members who enroll in select HMO and PPO plans in California and North Carolina1 will have access to Galleri beginning Jan. 1, 2022. Galleri is available by prescription only.

"GRAIL is thrilled to partner with Alignment Health Plan to offer our first-of-its-kind Galleri test to a population that by age alone has an elevated risk of developing cancer," said Dr. Josh Ofman, president and chief medical officer at GRAIL. "Providing access to a technology that can detect cancer signals in the blood, even before symptoms appear, can help us decrease the burden of late-stage cancer diagnoses. We commend Alignment for its innovative and proactive approach to early cancer detection for Medicare Advantage members."

In a clinical study, Galleri demonstrated the ability to detect more than 50 types of cancer, over 45 of which lack recommended screening tests today, with a low false positive rate of less than 1%. When cancer is detected, Galleri can determine the cancer signal origin with high accuracy.

More than 600,000 people died from cancer last year in the United States, according to the American Cancer Society. This is in large part because the majority of cancers are found too late when outcomes are often poor. Recommended screening tests save lives, but only cover five cancer types in the U.S.: breast, colon, cervical, prostate, and (in high-risk adults) lung. In fact, about seven in ten cancer deaths have no recommended early detection screening.

On December 6, 2021 Carisma Therapeutics., a clinical stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported that it has entered into a clinical study collaboration with Merck (known as MSD outside the US and Canada) to evaluate their proprietary targeted chimeric antigen receptor macrophages (CAR-M) in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) for the treatment of human epidermal growth factor receptor 2 (HER2) overexpressing cancers (Press release, Carisma Therapeutics, DEC 6, 2021, View Source [SID1234596529]).

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Based on pre-clinical findings outlined in Human chimeric antigen receptor macrophages for cancer immunotherapy, Carisma’s novel CAR-M platform has the potential ability to reprogram the solid tumor microenvironment, leading to immune activation, T cell recruitment, and anti-tumor adaptive immunity.

"The mechanisms of action behind CT-0508 and KEYTRUDA suggest they may be complementary and could help to drive meaningful clinical benefits in patients with HER2 positive cancers, where a high unmet medical need exists," said Steven Kelly, President and Chief Executive Officer at Carisma Therapeutics. "We are extremely pleased to enter into this collaboration with Merck and further expand the potential of macrophage-based cell therapy."

This collaboration announcement comes on the heels of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Anniversary Annual Meeting where lead investigators shared early data from the landmark Phase 1 multi-center clinical trial of CT-0508, a human epidermal growth factor receptor 2 (HER2) targeted CAR-M. The preliminary findings represent the first clinical data with genetically engineered macrophages in humans and demonstrated that CT-0508 was well tolerated after infusion and there were no dose limiting toxicities; data show the immunotherapy was successfully manufactured using macrophages obtained from heavily pre-treated, advanced solid tumor patients and showed high CAR expression, viability, and purity; and that the administered therapy remodeled the tumor microenvironment and mediated expansion/activation of T cells within the tumors.

Additional pre-clinical data generated by Carisma has shown the potential additive benefit of CAR-M in combination with PD-1 blockade in solid tumor models that are resistant to anti-PD-1 monotherapy.

The landmark CT-0508 clinical trial remains open for enrollment and the U.S. Food and Drug Administration recently granted Fast Track designation to CT-0508 for the treatment of patients with solid tumors. The clinical study evaluating CAR-M in combination with KEYTRUDA (pembrolizumab) is expected to launch in 2022.

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

On December 6, 2021 Bolt Biotherapeutics, Inc. (Nasdaq: BOLT), a clinical-stage biotechnology company pioneering a new class of immuno-oncology agents that combine the targeting precision of antibodies with the power of both the innate and adaptive immune systems, reported the presentation of interim clinical data from the company’s ongoing Phase 1/2 study of BDC-1001, the company’s lead immune-stimulating antibody conjugate (ISAC) in a poster session at the European Society for Medical Oncology Immuno-Oncology (ESMO I-O) Congress 2021, being held virtually from Dec. 6-11, 2021 (Press release, Bolt Biotherapeutics, DEC 6, 2021, View Source [SID1234596478]). The lead author for the poster is Manish Sharma, M.D., START Midwest, with contributions from Ecaterina Dumbrava, M.D., MD Anderson Cancer Center, and other colleagues from the U.S. and South Korea.

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The company reported data from 57 subjects participating in an ongoing Phase 1/2 study of BDC-1001, across 16 different types of HER2-expressing solid tumors. BDC-1001 demonstrated a favorable safety and tolerability profile at all evaluated doses and schedules, showing early signs of clinical activity with corresponding biomarker changes in the tumor microenvironment of post-treatment tumor biopsies. BDC-1001 is an immune-stimulating antibody conjugate (ISAC) comprising a HER2-targeting biosimilar of trastuzumab conjugated with a non-cleavable linker to an innovative TLR7/8 agonist.

"The favorable safety profile and early indications of clinical disease control in the BDC-1001 study are encouraging," said Dr. Sharma, Associate Director of Clinical Research at START Midwest. "There is a clear need for well tolerated, durable treatments in the fight against cancer and I’m excited to see if BDC-1001 can deliver on that potential as we explore higher drug exposure levels."

The poster presentation at ESMO (Free ESMO Whitepaper) I-O reported new safety, pharmacokinetic/pharmacodynamic, and efficacy results for the ongoing Phase 1 dose-escalation portion of the BDC-1001 monotherapy trial. Fifty-seven subjects have been treated at increasing dose levels up to 20 mg/kg every three weeks and 12 mg/kg every two weeks, and data from these subjects demonstrate that:

BDC-1001 continues to have a favorable safety and tolerability profile with mild (grade 1/grade 2) infusion related reactions in some patients and no dose-limiting toxicities at dose levels up to 20 mg/kg every three weeks and 12 mg/kg every two weeks. There was no indication of cytokine release syndrome (CRS), and a maximum tolerated dose (MTD) has not been reached.

Early signs of clinical activity are noted in 13 of 40 tumor evaluable subjects with one durable partial response maintained through 52 weeks and multiple subjects achieving stable disease for >12 weeks.

The pharmacokinetic (PK) data demonstrate increasing peak drug levels with increasing dose, and linearity of PK above the 5 mg/kg dose level. Clinical PK modeling predicts that target exposure levels can be achieved with weekly dosing.

Plasma and tissue biomarker results show increase in multiple biomarkers indicative of myeloid cell and TLR 7/8 activation that is consistent with BDC-1001’s mechanism of action. Increasing drug exposure correlates with increases in plasma cytokines and corresponding biomarker changes in the tumor microenvironment of multiple post-treatment tumor biopsies, with intriguing signs of clinical disease control.

These encouraging data point to the need for increased drug exposure to optimize clinical benefit. The favorable safety profile of BDC-1001 allows for continued enrollment in the dose escalation portion of the study, and the Company’s refined PK model based on data from more than 50 patients predicts that weekly administration will provide BDC-1001 exposures at or above the target exposure threshold. The data also support initiation of the combination therapy study with nivolumab (PD-1 inhibitor).

"Bolt Biotherapeutics is committed to agile clinical development based on data. In this Phase 1/2 study of BDC-1001, we have gained tremendous insight into the ability of this novel candidate to mobilize the patient’s immune system in targeting the tumor and its microenvironment. The increases in myeloid cell infiltration and repolarization of macrophages we’ve seen in multiple post-treatment biopsies are provocative and consistent with our proposed mechanism of action," said Edith Perez, M.D., Chief Medical Officer of Bolt Biotherapeutics. "We look forward to exploring weekly dosing as we get closer to determining the recommended Phase 2 dose for BDC-1001 as monotherapy, and to initiating combination therapy with a checkpoint inhibitor."

Presentation Details

Title: Preliminary results from a phase 1/2 study of BDC-1001, a novel HER2 targeting TLR7/8 immune-stimulating antibody conjugate (ISAC), in patients (pts) with advanced HER2-expressing solid tumors

Lead author: Manish R. Sharma, M.D.

Presentation Number: 164P

Timing: On-demand access beginning Dec. 6 at 12:00 p.m. CET.

The poster presentation will be available on the ESMO (Free ESMO Whitepaper) I-O conference website and on Bolt’s website.

Conference Call and Webcast Details

Bolt Biotherapeutics management will host a conference call for the investment community, in conjunction with the now virtual ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2021, to discuss emerging clinical data and insights from the ongoing Phase 1/2 study today, Monday, December 6, 2021, at 8:00 a.m. ET/5 a.m. PT.

The conference call can be accessed by dialing +1 (833) 665-0609 within the U.S. or Canada or by dialing +1 (929) 517-0400 from international locations. The passcode for the call is 2633068. A live webcast, including slides, will be available on the Events & Presentations page of Bolt Biotherapeutic’s website at www.boltbio.com. An archived replay can be accessed for 30 days following the webcast.

About the Boltbody Immune-Stimulating Antibody Conjugate (ISAC) Platform

ISACs are a new category of immunotherapy that combines the precision of antibody targeting with the strength of the innate and adaptive immune systems. Boltbody ISACs comprise three primary components: a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant to activate the patient’s innate immune system. By initially targeting a single marker on the surface of a patient’s tumor cells, an ISAC can create a new immune response by activating and recruiting myeloid cells. The activated myeloid cells start a feed-forward loop by releasing cytokines and chemokines, chemical signals that attract other immune cells and lower the activation threshold for an immune response. This reprograms the tumor microenvironment and invokes an adaptive immune response that targets the tumor, with the goal of durable responses for patients with cancer.

On December 6, 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 clinical data on its anti-CTLA-4 monoclonal antibody, ADG116, and anti-CD137 agonist, ADG106, in two poster presentations at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) Congress 2021, to be held virtually and in Geneva, Switzerland from December 8 to 11, 2021 (Press release, Adagene, DEC 6, 2021, View Source [SID1234596494]). Both posters are available in the Publications section of the company’s website at www.adagene.com.

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In the first presentation of results from an ongoing dose-escalation trial of monotherapy in patients with advanced metastatic tumors, ADG116 demonstrated a strong safety profile and early signals of efficacy, including dose-dependent T-cell activation and tumor suppression in treatment-resistant "cold" and "warm" tumors such as pancreatic, ovarian and renal cell cancers.

Commenting on the findings, Dr. Gary Richardson, OAM, MBBS, FRACP, Group Director at Cabrini Health Research, Director at Szalmuk Family Department of Medical Oncology and Professor of Medicine at Monash University, Australia, "These encouraging clinical data demonstrate the promising safety profile of ADG116 monotherapy in patients with advanced solid tumors across 15 different tumor types, the majority of which are resistant to standard therapy. The most exciting thing about these results is that we have also seen the early signals of efficacy in ‘cold’ tumors such as pancreatic and certain gynecological cancers, which do not respond to current immunotherapies. We want to see this type of unique activity, which suggests that this treatment may look different and potentially better than the options we have available today."

Additionally, a separate poster presentation describing results of pharmacodynamic (PD) biomarker analyses reinforced the synergy and strong T-cell activation of ADG106 in combination with the anti-PD-1 antibody toripalimab.

A summary of data from both posters is included below.

ADG116

Key findings from the poster (#137P) titled "Phase 1 dose-finding study of a novel anti–CTLA-4 antibody ADG116 as monotherapy in patients with advanced solid tumors" include:

Clinical results from a global dose escalation and cohort expansion trial with sites in the U.S. and Australia (ADG116-1003) evaluated ADG116 monotherapy in 25 heavily pre-treated patients with advanced metastatic solid tumors, the majority of which are insensitive to immunotherapy:
Patients across 15 different tumor types were evaluated.
The majority (68 percent) received three or more lines of prior systemic therapy.
Nearly one quarter (24 percent) received prior immunotherapy treatment.
ADG116 monotherapy was well-tolerated up to 6 mg/kg with only Grade 1 or 2 treatment-related adverse events (TRAEs) observed; rash (20 percent) and pruritus (20 percent) were the most common.
In the ongoing 10 mg/kg cohort, a rash (Grade 3) and dose limiting toxicity event (Grade 4 hyperglycemia) occurred in a patient with renal cell carcinoma who relapsed on nivolumab. A significant increase in the patient’s CD8 T cells after one cycle of treatment showed that ADG116 is highly active for triggering T cell activation.
ADG116 treatment resulted in dose-dependent increases in peripheral CD8 and CD4 T cells, indicating immune activation by targeting the CTLA-4 pathway, starting at a dose as low as 0.03 mg/kg and becoming more striking at the 6 mg/kg and 10 mg/kg dose levels. In one example, a patient refractory to multiple cycles of pembrolizumab treated at 0.03 mg/kg showed increased CD8 and CD4 T cells.
In the dose escalation portion of the trial, four prolonged stable diseases were observed amongst these heavily pre-treated patients.
Of special note is a 22 percent tumor reduction observed in target lesions (after the data cut-off on October 15, 2021) following two cycles of ADG116 for a pancreatic cancer patient treated at 10 mg/kg. Only Grade 1 TRAEs were observed and the patient’s non-target lesion (23 x 12mm) disappeared. The patient continues on treatment.
Additionally, an ovarian cancer patient treated at 6mg/kg showed stable disease for more than 116 days with increased CD8 and CD4 T cells. The patient continues on treatment.
ADG116 demonstrated dose-proportional increases in drug exposure with a half-life supporting convenient dosing every three weeks.
The findings support that ADG116 has achieved the recommended dosing range as a single agent and for evaluation in combination therapy. The ADG116-1003 trial continues with dose escalation at 10 mg/kg, while cohort expansion has been initiated at 6 mg/kg.

Adagene is also advancing ADG116 in combination with anti-PD-1 therapy (pembrolizumab or toripalimab) and with its proprietary anti-CD137 agonist (ADG106). Further, the company is evaluating a second anti-CTLA-4 antibody, ADG126, using its SAFEbody precision masking technology in an ongoing phase 1 dose escalation as monotherapy. This reflects the company’s commitment to unlock the value of CTLA-4 as a proven target and the backbone of future immunotherapies.

ADG106

Key findings from the poster (#43P) titled "Assessment of Biomarker Kinetics for ADG106 (anti-CD137 agonist) as monotherapy or combined with toripalimab" include:

Results of PD biomarker analyses which demonstrated the synergistic effect of ADG106 in combination with an anti-PD-1 antibody, toripalimab, compared to ADG106 monotherapy at doses up to 3 mg/kg.
The combination of ADG106 with toripalimab resulted in a 2-fold greater immune activation versus ADG106 alone. These results were observed even amongst patients who failed prior anti-PD-1 and CTLA-4 therapies.
Soluble CD137 levels (sCD137) levels increased with immune activation suggesting this as a dose-dependent PD biomarker of T cell target engagement, which could be used to monitor potential clinical response.
ADG106 treatment alone and in combination with anti-PD-1 therapy also increased serum IFN-γ, IL-6, natural killer cells, and T-cell subsets.
Additional analyses demonstrate that the pharmacokinetic profile of ADG106 was not altered by the addition of toripalimab.
These findings highlight the synergistic activity of ADG106 in combination with the anti-PD-1 toripalimab for patients who failed anti-PD-1 and anti-CTLA-4 immunotherapies. This combination is being evaluated in the ongoing ADG106-1008 clinical trial, currently in a cohort dosing ADG106 at 3 mg/kg. The data support further exploration of combination therapy regimens with ADG106 at informed dose ranges for targeting biomarker enriched tumor types.

"The data presented today from two of our NEObody clinical programs show how we are creating transformative antibody-based immunotherapies that push the limits of antibody discovery and development, overcoming liabilities with some of the most promising yet challenging immuno-oncology targets today," said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene. "These findings strengthen confidence in our clinical pipeline and in the ability of our platform technologies to achieve unprecedented results that will ultimately benefit patient care."

About ADG116

This NEObody program, targeting a unique epitope of CTLA-4, is being evaluated in patients with advanced/metastatic solid tumors. ADG116 is designed to enhance efficacy by potent Treg depletion in the tumor microenvironment (TME) and maintain its physiological function by soft ligand blocking to address safety concerns associated with existing CTLA-4 therapeutics.

About ADG106

This NEObody program is a fully human ligand-blocking, agonistic anti-CD137 IgG4 monoclonal antibody (mAb) that is being evaluated in patients with advanced solid tumors and/or non-Hodgkin’s lymphoma.

On December 6, 2021 Novocure (NASDAQ: NVCR) reported the 4th Annual AACR (Free AACR Whitepaper)-Novocure Grants for Tumor Treating Fields Research Program. The program represents a joint effort with the American Association for Cancer Research (AACR) (Free AACR Whitepaper) to promote and support innovative research on Tumor Treating Fields (TTFields) to help deepen the understanding of the mechanism of action and to accelerate the development of new treatment strategies (Press release, NovoCure, DEC 6, 2021, View Source [SID1234596510]). The program includes research grants and career development awards totaling more than $2 million over the next three years.

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The research grants will include five AACR (Free AACR Whitepaper)-Novocure Tumor Treating Fields Research Grants and two AACR (Free AACR Whitepaper)-Novocure Career Development Awards for Tumor Treating Fields Research. Recipients of the research grants will receive a total of $250,000 over two years. Recipients of the career development awards will receive a total of $225,000 over three years.

"We are thrilled to continue our partnership with Novocure," said Mitch Stoller, the AACR (Free AACR Whitepaper)’s Chief Philanthropic Officer. "These two grant mechanisms represent an important means for advancing the science of TTFields research and attracting talented investigators. We once again look forward to learning about the outstanding projects that will result from these grants and to meeting next year’s class of grantees."

Novocure and the AACR (Free AACR Whitepaper) encourage applicants to focus their proposals on translational approaches, promoting the transition of in vitro work into in vivo systems; combination therapies involving Tumor Treating Fields; and bringing treatments involving Tumor Treating Fields to the clinic. The application deadline is January 20. Recipients will be announced in April at the AACR (Free AACR Whitepaper) Annual Meeting 2022 in New Orleans.

"Deepening our understanding of the mechanism of action of Tumor Treating Fields can potentially advance our efforts to extend survival in some of the most aggressive forms of cancer," said Dr. Uri Weinberg, Novocure’s Chief Science Officer. "We are excited to partner with the AACR (Free AACR Whitepaper) to offer this innovative research program for the fourth year and look forward to the announcement of recipients at the AACR (Free AACR Whitepaper) Annual Meeting."

To apply for the AACR (Free AACR Whitepaper)-Novocure Grants for Tumor Treating Fields Research, visit www.aacr.org/funding.

About Tumor Treating Fields

Tumor Treating Fields, or TTFields, are electric fields that disrupt cancer cell division. Fundamental scientific research on TTFields extends across more than two decades and, in all preclinical research to date, TTFields have demonstrated a consistent anti-mitotic effect. TTFields therapy is intended principally for use together with other standard-of-care cancer treatments. There is a growing body of evidence that supports TTFields’ broad applicability with certain other cancer therapies, including radiation therapy, certain chemotherapies and certain immunotherapies. In clinical research and commercial experience to date, TTFields therapy has exhibited no systemic toxicity, with mild to moderate skin irritation being the most common side effect. The TTFields global development program includes a network of preclinical collaborators and a broad range of clinical trials across all phases, including four phase 3 pivotal trials in a variety of tumor types. To date, more than 20,000 patients have been treated with TTFields therapy.