On November 12, 2021 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported that three posters with preclinical data of its innate cell engagers (ICE) are presented at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Affimed, NOV 12, 2021, View Source [SID1234595442]). The data highlight Affimed’s preclinical initiatives to further elucidate the mechanisms of action for its lead ICE candidates AFM13 and AFM24, providing evidence that both ICE molecules increased the number of NK cells which functioned as serial killers against cancer as well as the role of macrophages in the anti-tumor activity of AFM24.

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The poster based on abstract 894 displays data generated through a collaboration with Prof. Björn Önfelt’s group at the Karolinska Institutet, Stockholm. In the study, microchip technology was used for two ICE drug candidates, AFM13 and AFM24, at single cell resolution to better understand their mode of action. Both ICE molecules enhanced NK cell cytotoxicity and increased the number of serial killers, i.e. NK cells which kill a number of tumor cells sequentially. Shedding inhibition of the innate immune cell surface protein CD16 resulted in the maintained cytotoxic effect of either ICE molecule demonstrating that stabilization of CD16 is not required for effective tumor cell killing by ICE drug candidates. "Showing serial killing for AFM13- and AFM24-engaged NK cells in single cell resolution is impressive," said Prof. Björn Önfelt. "The microchip technology visualizes the cytotoxicity of AFM13- and AFM24-engaged NK cells and demonstrates that ICE activated NK cells can lead to multiple tumor cell killings by a single NK cell."

Two additional posters (abstracts 880 and 881) present data on AFM24’s ability to induce antibody dependent cellular phagocytosis (ADCP). AFM24, the bispecific ICE targeting EGFR and CD16A, led to enhanced macrophage-mediated ADCP on various EGFR-expressing tumor cell lines, irrespective of their EGFR-pathway mutational status.

To refine the prediction of in vivo tumor responses to AFM24, Affimed has established 2D and 3D assay conditions in patient-derived xenograft (PDX) cell lines. The 3D model is designed to replicate intrinsic physiological conditions. Early results show that AFM24 can induce ADCP in tumor cells in 2D PDX cell cultures, engaging M0, M1 and M2 macrophage subsets context-dependently. ADCP is potentially instrumental for AFM24’s mechanism of action, especially in macrophage-rich tumors.

"Our ICE AFM24 is in development for a number of solid tumor indications," said Dr. Arndt Schottelius, CSO of Affimed. "Considering that many solid tumors are rich in macrophages, it is very encouraging to see what role ADCP plays in its mechanism of action. The newly established 2D and 3D models will help to predict responses to AFM24 in certain tumor types."

AFM24 is currently investigated as monotherapy in a Phase 1/2a study in patients with EGFR-expressing solid tumors in need of alternative treatment options. In addition, Affimed and NKGen Biotech have initiated a clinical study to investigate AFM24 in combination with NK cells. Affimed expects to initiate an additional clinical study with an anti-PD-L1 checkpoint inhibitor before the end of 2021.

For the full abstracts, please go https://bit.ly/3HgWlIa. The posters can be found at View Source

About AFM13
AFM13 is a first-in-class innate cell engager (ICE) that uniquely activates the innate immune system to destroy CD30-positive hematologic tumors. AFM13 induces specific and selective killing of CD30-positive tumor cells, leveraging the power of the innate immune system by engaging and activating natural killer (NK) cells and macrophages. AFM13 is Affimed’s most advanced ICE clinical program and is currently being evaluated as a monotherapy in a registration-directed trial in patients with relapsed/refractory peripheral T-cell lymphoma or transformed mycosis fungoides (REDIRECT). The study is actively recruiting. Additional details can be found at www.clinicaltrials.gov (NCT04101331).
In addition, The University of Texas MD Anderson Cancer Center is studying AFM13 in an investigator-sponsored Phase 1 trial in combination with cord blood-derived allogeneic NK cells in patients with recurrent or refractory CD30-positive lymphomas (NCT04074746).

About AFM24
AFM24 is a tetravalent, bispecific innate cell engager (ICE) that activates the innate immune system by binding to CD16A on innate immune cells and EGFR, a protein widely expressed on solid tumors, to kill cancer cells. Generated by Affimed’s fit-for-purpose ROCK platform, AFM24 represents a distinctive mechanism of action that uses EGFR as a docking site to engage innate immune cells for tumor cell killing through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Affimed is evaluating AFM24 as a monotherapy (AFM24-101) for patients with advanced EGFR-expressing solid malignancies whose disease has progressed after treatment with previous anticancer therapies. Details about the first-in-human Phase 1/2a open-label, non-randomized, multi-center, multiple ascending dose escalation and expansion study and can be found at www.clinicaltrials.gov (NCT04259450).
In 2021, Affimed also aims to initiate a Phase 1/2a study (AFM24-102), evaluating AFM24 in combination with Roche’s atezolizumab, an anti-PD-L1 checkpoint inhibitor. A Phase 1/2a study (AFM24-103) of AFM24 in combination with NKGen Biotech’s autologous NK cell product, SNK01, has recently been initiated.

On November 12, 2021 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported positive preclinical data from CDX-585, the Company’s bispecific antibody with dual targeting of ILT4 and PD-1 checkpoint pathways, developed from its bispecific antibody platform (Press release, Celldex Therapeutics, NOV 12, 2021, View Source [SID1234595441]). These data were presented in a poster session as part of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 36th Annual Meeting (SITC 2021).

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The data show CDX-585 effectively combines the blockade of ILT4 and PD-1 into one molecule, with favorable biophysical and functional characteristics, supporting the initiation of development activities including manufacturing and IND-enabling studies. CDX-585 is the first compound from Celldex’s research and collaboration agreement with Biosion, Inc. and combines Celldex’s ILT4 mAb with Biosion’s PD-1 mAb.

"We are pleased with this data which demonstrate we have successfully combined two important pathways into one molecule and support the further advancement of CDX-585," said Tibor Keler, Ph.D., Executive Vice President and Chief Scientific Officer of Celldex Therapeutics. "We believe that co-targeting ILT4 and PD-1, which are both critical checkpoint pathways, has the potential to produce significant immune enhancing and antitumor effects. We are excited to move forward with CDX-585 in addition to the continued generation of other candidates from our bispecific antibody platform for oncology and inflammatory diseases."

In the preclinical data presented at SITC (Free SITC Whitepaper), the simultaneous inhibition of ILT4 and PD-1 checkpoints with CDX-585 led to myeloid and T cell activation which may potentially demonstrate clinical utility, particularly in the T cell checkpoint inhibitor refractory setting. CDX-585 promoted T cell activation as measured by mixed lymphocyte reactions superior to that achieved by the combination of ILT4 and PD-1 monoclonal antibodies. CDX-585 also demonstrated anti-tumor activity in a humanized mouse model of melanoma and had a favorable pharmacokinetic profile in pilot studies, without adverse effects of treatment noted in clinical observations or clinical chemistry.

The poster presented at SITC (Free SITC Whitepaper) can be viewed on the "Publications" page of the "Science" section of the Celldex website.

About CDX-585
CDX-585 is a dual targeting PD-1/ILT4 bispecific antibody from Celldex’s bispecific antibody platform, currently in preclinical studies including manufacturing and IND-enabling studies. Expression of ILT4 in several tumor types is associated with poor outcome and in preclinical models, antagonist antibodies to ILT4 have demonstrated immune enhancing and antitumor effects. CDX-585 is being developed as part of a research and collaboration agreement with Biosion, Inc.

About Celldex’s Bispecific Antibody Platform
Celldex’s deep antibody experience and in-house manufacturing capabilities support efficient development of next generation bispecific antibody programs for inflammatory/autoimmune diseases and oncology. Bispecific antibodies can engage two independent pathways involved in controlling immune reactions and combining these into one molecule can result in stronger activity than a combination of the independent antibodies. Targets are being selected based on new science as well as their compatibility to be used in bispecific antibody formats with Celldex’s existing antibody programs. Lead targets in development are emerging as important pathways controlling inflammatory diseases or immunity to tumors.

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.