On November 12, 2021 Agenus (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of checkpoint antibodies, adjuvants, and vaccines designed to activate immune response to cancers and infections, reported the presentation of new clinical data for AGEN1181 (Fc-enhanced anti-CTLA-4) as monotherapy and in combination with balstilimab (anti-PD-1) at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting (Press release, Agenus, NOV 12, 2021, View Source [SID1234595440]).

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"AGEN1181 as monotherapy and in combination with balstilimab has shown durable responses in heavily pre-treated, poorly immunogenic ‘cold’ cancers, as well as those who have failed to respond to prior PD-1 inhibition," said Steven O’Day, MD, Chief Medical Officer of Agenus. "This regimen is well tolerated, with no hypophysitis, pneumonitis, or high-grade hepatitis observed to date. The clinical performance of AGEN1181 is consistent with its Fc-enhanced design, safely expanding the benefit of immunotherapy to a broader patient population."

Evidence of single agent activity
As of the data cut-off date of September 17, 2021, one hundred and sixteen patients received AGEN1181 in a dose escalation study to determine the optimal monotherapy dose and combination dose with balstilimab. Of note, this population was heavily pre-treated, with over half of these patients receiving at least 3 prior lines of therapy and nearly a third of patients receiving prior anti-PD-1 therapy. There were four cases of confirmed objective responses to AGEN1181 monotherapy. These include a complete response (CR) in MSS endometrial cancer, and partial responses (PR) in pancreatic cancer, as well as PD-1 refractory cervical cancer. These are the first reported responses to CTLA-4 monotherapy in these disease settings. The fourth response was in a patient with PD-1 refractory melanoma. Of note, three of the monotherapy responders expressed the low affinity FcγRIIIA receptor, which is associated with lack of response to first-generation CTLA-4 inhibitors1.

Balstilimab combination benefits >60% of patients
Significant benefit was also observed with the combination of AGEN1181 and balstilimab across multiple "cold" cancers studied, with >60% of evaluable patients receiving at least 1 mg/kg AGEN1181 experiencing disease control. Among 20 evaluable patients with microsatellite stable colorectal cancer (MSS-CRC), where PD-1 inhibitors have historically shown limited to no activity2-5, there were three confirmed PRs and one unconfirmed PR. In addition, ten cases of stable disease (SD) were observed, with one patient’s tumor burden reduced by 27%. The disease control rate (DCR) among these MSS CRC patients was 70%.

Among 9 evaluable ovarian cancer patients receiving at least 1 mg/kg of AGEN1181 in combination with balstilimab, there were three confirmed PRs and two cases of SD (one of the patients with SD had a 28% reduction of tumor burden). Compelling clinical activity was also seen in MSS-endometrial cancer as both patients treated with combination therapy demonstrated PRs; all three patients with MSS endometrial cancer treated with AGEN1181 (one with monotherapy, two in combination with balstilimab) had objective responses. Additional responders to combination therapy include 1 confirmed PR in a NSCLC patient who failed prior PD-1 therapy, 2 confirmed PRs in visceral angiosarcoma, and 1 unconfirmed PR in leiomyosarcoma.

Responses in this Phase 1 trial have been durable, with half lasting at least 24 weeks and the majority ongoing.

"AGEN1181 as monotherapy and in combination with balstilimab has shown promising activity in patients with poorly immunogenic tumors such as MSS-CRC, endometrial and ovarian cancers; these are tumor types that do not traditionally respond well to single agent anti PD-1/PD-L1 therapy," said Anthony El-Khoueiry, MD, Phase I Program Director and Associate Professor of Clinical Medicine at Keck School of Medicine of University of Southern California (USC). Dr. El-Khoueiry is also an oncologist at the USC Norris Comprehensive Cancer Center, part of Keck Medicine of USC. "Importantly, multiple responders expressed the low affinity FcγRIIIA receptor, a feature that makes them less likely to respond to first-generation CTLA-4 antibodies. Together, this highlights the potential of AGEN1181 to fulfill unmet medical needs in the current treatment landscape by overcoming limitations of approved immunotherapies."

Differentiated safety profile versus first generation CTLA-4 inhibitors
AGEN1181 was well tolerated with no hypophysitis, pneumonitis, or high-grade hepatitis. Rates of gastrointestinal and skin toxicities were comparable to those observed with first-generation CTLA-4 inhibitors.

Phase 2/3 trials to be initiated in colorectal and gynecological cancers
Based on these data, multi-arm, randomized phase 2/3 trials investigating AGEN1181 as monotherapy and in combination with balstilimab in MSS-CRC and gynecological cancers (ovarian and MSS-endometrial cancer) are being initiated. The design of these trials may support a potential filing for full and/or accelerated approval based on the magnitude of benefit demonstrated in the studies. Combination studies of AGEN1181 with AGEN2373, a conditionally active CD137 agonist, are expected to begin later this year in PD-1 refractory melanoma.

Presentation Details:
Abstract Title: AGEN1181, an Fc-enhanced anti-CTLA-4 antibody, alone and in combination with balstilimab (anti-PD-1) in patients with advanced solid tumors: Initial phase I results (NCT03860272)
Abstract Number: 479
Presenting Author: Dr. Anthony El-Khoueiry

The poster presentation can be accessed in the investor section of our website at View Source

In addition, Dr. Steven O’Day, Chief Medical Officer at Agenus and Dr. Manuel Hidalgo, Chief of the Division of Hematology and Medical Oncology at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center, will participate in a webcast hosted by Dr. Matt Phipps, biotechnology analyst at William Blair on Friday, November 12, 2021 at 12:00 p.m. ET.

Registration for the webinar can be done in advance at View Source

A replay will be available after the call for 30 days on the Events & Presentations page of the Agenus website at View Source

Disclosures:
Dr. El-Khoueiry has served as a consultant for Agenus.

About AGEN1181
AGEN1181 is a next-generation, Fc-enhanced, immunoglobulin G1 (IgG1) antibody designed to block CTLA-4 (cytotoxic T-lymphocyte associated antigen 4) from interacting with its ligands CD80 and CD86. The Fc region of the antibody was engineered to enhance potency, improve safety, and benefit a broader patient population versus first-generation anti CTLA-4 antibodies. CTLA-4 is a negative regulator of immune activation that is considered a foundational target within the immuno-oncology market.

About Balstilimab
Balstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4) designed to block PD-1 (programmed cell death protein 1) from interacting with its ligands PD-L1 and PD-L2. PD-1 is a negative regulator of immune activation that is considered a foundational target within the immuno-oncology market.

On November 12, 2021 Bavarian Nordic A/S (OMX: BAVA) reported its interim financial results for the first nine months of 2021 and business progress for the third quarter of 2021 (Press release, Bavarian Nordic, NOV 12, 2021, View Source [SID1234595439]).

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Paul Chaplin, President & Chief Executive Officer of Bavarian Nordic said: "We continued to experience a challenging market environment for our travelers vaccine business during the third quarter, due to COVID-19. Despite these headwinds, we remain on track to meet our guidance as both our smallpox and Ebola vaccine sales remain unaffected. This truly highlights the importance of a broader and more diversified product portfolio. We are very pleased with the strong pipeline progress seen during the quarter, where highly promising results for our COVID-19 booster vaccine candidate were reported and funding for the remaining phases was secured. Likewise, we have presented strong results for our RSV vaccine candidate, which showed remarkable efficacy in reducing symptomatic RSV infections in a challenge study. These assets provide an encouraging outlook for Bavarian Nordic, and we look forward to providing more updates as the work progresses."

Financial highlights

Total revenue in the first nine months was DKK 1,354 million comprised of DKK 1,323 million from combined product sales and DKK 31 million from contract work.
Revenue in the third quarter totaled DKK 449 million comprised of DKK 214 million from sales of MVA-BN smallpox vaccine, DKK 160 million from sales of Rabipur/RabAvert, DKK 72 million from sales of Encepur and DKK 3 million from contract work.
EBITDA in the first nine months was DKK 44 million.
Strong cash position of DKK 2,182 million** at the end of the period.
Full-year guidance maintained with expected revenue of approximately DKK 1,900 million, EBITDA of approximately DKK 100 million and securities, cash and cash equivalents at year-end of approximately DKK 1,400 million.

EBITDA in the first nine months of 2020 was positively impacted by the sale of the Priority Review Voucher (DKK 628 million).
** Unutilized credit facilities of DKK 243 million not included. Repo pledged securities deducted.

Other highlights

In August, initial results from the first-in-human trial of the COVID-19 vaccine candidate, ABNCoV2 were reported, which demonstrated that the vaccine candidate was well tolerated and induced a strong antibody response, higher than currently approved vaccines. Results from the high dose groups are now available and suggest a plateau in the responses as similar high antibody titers were shown for these groups. Importantly, a strong neutralization response was demonstrated against SARS-CoV-2 variants, including the Delta variant.
In August, Bavarian Nordic initiated a phase 2 clinical trial of ABNCoV2 to investigate the vaccine’s potential as a universal booster vaccine for individuals with existing immunity from prior COVID-19 disease or vaccination. Initial results from the study are expected in December 2021.
In August, Bavarian Nordic entered a funding agreement with the Danish Ministry of Health, under which the Company will be eligible to receive up to DKK 800 million to further advance the development of ABNCoV2 as a booster vaccine for COVID-19. The agreement was finally executed in September upon approval from the Finance Committee of the Danish Parliament.
In September, Bavarian Nordic reported positive results from the human challenge trial of MVA-BN RSV. The trial achieved the primary endpoint of the pivotal study by demonstrating a statistically significant reduction in viral load in vaccinated versus control (placebo) treated volunteers. The vaccine demonstrated a 79% efficacy in reducing symptomatic RSV infections. Preparations for a phase 3 trial in 2022 continue, pending a final decision driven by regulatory discussions and feedback on the trial design and funding/partnering considerations.
Events after the reporting date

In accordance with the shareholder authorization for the board of directors and the Company’s remuneration policy, the board of directors has today decided to issue warrants to executive management and certain employees in the Bavarian Nordic Group. In accordance with the Company’s remuneration policy, President and CEO, Paul Chaplin will receive an extraordinary grant as further explained on page 6 in the interim report. A total of 716,256 warrants have been issued, which entitle the warrant holders to subscribe for up to 716,256 shares in total, with a nominal value of DKK 10 each at an exercise price of DKK 353.06 per share.
Conference call and webcast
The management of Bavarian Nordic will host a conference call today at 2 pm CET (8 am EST) to present the interim results followed by a Q&A session. A listen-only version of the call can be accessed via View Source To join the Q&A session, use one of the following dial-in numbers: Denmark: +45 32 72 80 42, UK: +44 (0) 844 571 8892, USA: +1 631-510-7495. Participant code is 2839609.

Contacts
Europe: Rolf Sass Sørensen, Vice President Investor Relations, Tel: +45 61 77 47 43
US: Graham Morrell, Paddock Circle Advisors, [email protected], Tel: +1 781 686 9600

Company Announcement no. 35 / 2021

On November 12, 2021 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage, precision oncology biopharmaceutical company, reported that Susan Molineaux, Ph.D., the company’s founder, president and chief executive officer, will present at the 2021 Jefferies London Healthcare Conference (Press release, Calithera Biosciences, NOV 12, 2021, View Source [SID1234595428]).

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The presentation will be available for on-demand viewing starting Thursday, November 18 at 3:00 a.m. Eastern Time, and can be accessed through the Investors section of the Company’s website at www.calithera.com. The replay of the webcast will be available on the Company’s website for 30 days.

On November 12, 2021 Silverback Therapeutics, Inc. (Nasdaq: SBTX) ("Silverback"), a clinical-stage biopharmaceutical company leveraging its proprietary ImmunoTAC technology platform to develop systemically delivered, tissue targeted therapeutics for the treatment of cancer, chronic viral infections, and other serious diseases, reported a trial-in-progress poster on SBT6050-201 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting, held virtually from November 10-14, 2021 (Press release, Silverback Therapeutics, NOV 12, 2021, View Source [SID1234595411]). SBT6050-201 is a Phase 1/2 study evaluating SBT6050 in combination with trastuzumab deruxtecan (Enhertu), or with trastuzumab (Herceptin) and tucatinib (Tukysa) with or without capecitabine, in patients with HER2-expressing or HER2-amplified gastroesophageal, non-small cell lung, breast, and colorectal cancers.

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"SBT6050 was designed to enable combinations with trastuzumab-containing regimens, which are foundational in the standard of care for HER2-positive solid tumors," said Naomi Hunder, M.D., chief medical officer of Silverback Therapeutics. "There is compelling scientific and clinical rationale to combine SBT6050 with these regimens. Importantly, in addition to the trastuzumab component of these regimens, they each contain a cytotoxic component that drives immunogenic cell death, releasing tumor neoantigens. SBT6050 activates dendritic cells, potentially enhancing neoantigen presentation to T cells and amplifying the anti-tumor response. SBT6050 may also enhance trastuzumab-mediated antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. We look forward to initiating clinical evaluation of these combinations in the first quarter of 2022."

The poster is now available on the SITC (Free SITC Whitepaper) website and on the Silverback website here. Details are as follows:

Poster Title: A phase 1/2 study of SBT6050 combined with trastuzumab deruxtecan (T-DXd) or trastuzumab and tucatinib with or without capecitabine in patients with HER2-expressing or HER2-amplified cancers
Presenter: Sam J. Klempner, MD
Category: Clinical Trials in Progress
Abstract Number: 393

About SBT6050

SBT6050 is the first of a new class of targeted immuno-oncology agents designed to direct a TLR8 agonist linker-payload to activate myeloid cells in tumors expressing moderate to high levels of HER2. TLR8 is expressed in myeloid cell types prevalent in human tumors and TLR8 agonism can activate a broad spectrum of anti-tumor immune mechanisms, including pathways involved in the innate and adaptive immune response. SBT6050 was specifically designed to bind to the HER2 sub-domain II, the pertuzumab epitope, to enable combinations with trastuzumab-containing therapies. SBT6050 is currently being evaluated in a Phase 1/1b trial in patients with advanced or metastatic HER2-expressing or amplified solid tumors.

On November 12, 2021 Sensei Biotherapeutics, Inc. (NASDAQ: SNSE), an immunotherapy company focused on the discovery and development of next generation therapeutics for cancer, reported the first preclinical data for SNS-101, its anti-VISTA (V-domain Ig suppressor of T cell activation) product candidate (Press release, Sensei Biotherapeutics, NOV 12, 2021, View Source [SID1234595410]). The data will be presented during a poster session on November 13, 2021, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC 2021) 36th Annual Meeting in Washington, D.C. and virtually .

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"VISTA has been recognized for years as an important immune checkpoint but has been difficult to drug due to its unique pH-dependent biology," said Robert Pierce, M.D. chief scientific officer of Sensei Biotherapeutics. "VISTA is primarily expressed on myeloid cells, a hub of immunosuppressive activity, and functions as a checkpoint exclusively under acidic conditions where it binds to its receptor, PSGL-1. Our scientific team has been evaluating VISTA for several years. Accordingly, we believe, the key to unlocking the power of this checkpoint lies with the development of an antibody that selectively binds the active form of VISTA that is only present within the low pH of the tumor microenvironment. At SITC (Free SITC Whitepaper), we are excited to share the preclinical data demonstrating that SNS-101 binds active VISTA with high affinity and significant selectivity (~600-fold increase at pH 6.0 versus 7.4)."

Dr. Pierce continued, "We are also encouraged by early in vivo evidence from a human VISTA knock-in mouse model showing improved immune responses, including the anticipated combination effect with anti-PD1 in a PD1 blockade responsive tumor model. We continue to expand on this research and are looking forward to sharing more in vivo data at a future medical conference. IND-enabling studies are already underway to evaluate the potential of SNS-101 to become a novel treatment for solid cancers, as both a monotherapy and in combination, that overcomes on-target/off-tumor toxicities seen today with other I/O approaches."

Preclinical data for SNS-101 are being presented in a poster (#228) titled: "Antagonistic pH-selective VISTA antibody SNS-101 potentiates anti-PD-1/PD-L1-induced anti-tumor immunity." A summary of data in the poster include:

Preclinical data demonstrated that SNS-101 successfully blocked the interaction of VISTA with its PSGL-1 receptor, demonstrating high-affinity binding to low pH-VISTA sub-nanomolar affinity with exemplary (>600-fold) pH-selectivity vs. physiologic pH-VISTA.
SNS-101, in combination with an anti-PD-1 inhibitor, led to superior anti-tumor activity compared to PD-1 alone.
SNS-101 is a fully human IgG1 and has entered IND-enabling studies.
Sensei will host a virtual science symposium on Tuesday, November 16, 2021, at 4:00 p.m. Eastern Time to discuss the potential of the VISTA checkpoint inhibitor to address current limitations of immune checkpoint therapy. The event will be hosted by Sensei’s management team and will include a presentation on VISTA biology by Robert Schreiber, Ph.D., the Andrew M. Bursky and Jane M. Bursky Distinguished Professor of Pathology and Immunology, Professor of Molecular Microbiology and co-leader of the tumor immunology program at the Siteman Comprehensive Cancer Center and Founding Director of the Center for Human Immunology and Immunotherapy Programs at the Washington University School of Medicine.

A live webcast of the symposium will be available under "Events & Presentations" in the Investors section of the company’s website at www.senseibio.com. An archived replay will be available for approximately 90 days following the event.

About VISTA (V-domain Ig suppressor of T cell activation)

VISTA (B7-H5) is recognized as an important immune checkpoint regulator that is expressed primarily on myeloid cells, a hub of immunosuppressive activity, and acts via binding to its receptor on T-cells (PSGL-1) at sub physiologic pH. Disrupting the interaction of VISTA and its receptor on T-cells has been shown to enhance T-cell activation and tumor cell death. The VISTA-PSGL-1 T-cell checkpoint is activated under low pH conditions such as the tumor microenvironment. VISTA is found to be expressed in numerous cancer types and appears to be associated with PD-1 resistance.

The therapeutic hypothesis that Sensei believes differentiates its VISTA program is that an effective and safe inhibitory anti-VISTA antibody must demonstrate: (1) selective binding to the active form of VISTA (protonated/low pH) in order to avoid target mediated drug disposition and on-target/off-tumor effects; (2) effective inhibition of active VISTA’s interaction with PSGL-1; and (3) Fc-mediated activation of tumor resident myeloid cells to facilitate conversion from an immunosuppressive to an immune-activating phenotype.

About SNS-101
SNS-101 is a potent, pH-dependent fully human monoclonal antibody designed to block the interaction of VISTA, a novel immune checkpoint that is expressed primarily on myeloid cells, with its receptor, PSGL-1. Selectivity is achieved because SNS-101 targets the active (i.e., protonated) VISTA present in the low pH tumor microenvironment. SNS-101 was selected based on 1) the lack of significant binding to VISTA at physiologic pH (i.e., deprotonated VISTA in the blood), and 2) its high-affinity binding to active VISTA (pH 6.0), which yielded a > 600-fold selectivity. Based on the biochemical properties of SNS-101, Sensei anticipates tumor microenvironment selective activity for this preclinical product candidate. VISTA has been shown to be expressed in numerous tumor types, including non-small cell lung cancer (NSCLC).