On November 15, 2021 Celsion Corporation (NASDAQ: CLSN), a clinical-stage drug-development company focused on DNA-based immunotherapy and next-generation vaccines, reported financial results for the three and nine months ended September 30, 2021, and provided an update on clinical development programs with GEN-1, a DNA-based interleukin-12 (IL-12) immunotherapy in Phase II clinical development for the treatment of advanced-stage ovarian cancer (Stage III/IV), and ThermoDox, a proprietary heat-activated liposomal encapsulation of doxorubicin under investigator-sponsored development for several cancer indications (Press release, Celsion, NOV 15, 2021, View Source [SID1234595584]). In addition, Celsion has two feasibility-stage platform technologies for the development of novel nucleic acid-based immunotherapies and next-generation vaccines for infectious diseases.

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"GEN-1 continues to show momentum as patient enrollment nears 70% with full enrollment targeted by the first half of 2022. We are encouraged with surgical resection results at the 100 mg/m² dose cohort in the Phase II OVATION 2 Study. From the first 36 patients with interval debulking surgery, 80% treated with GEN-1 at a dose of 100 mg/m² plus neoadjuvant chemotherapy (NACT) had a complete tumor resection (R0), which indicates a microscopically margin-negative resection with no gross or microscopic tumor remaining in the tumor bed; this compares with 56% of patients in the control arm having R0 resections. These results are reasonably consistent with those reported from our earlier Phase I trials in advanced-stage ovarian cancer," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer.

"At the International Vaccines Congress in October, Celsion announced results from preclinical in vivo studies showing production of antibodies and cytotoxic T-cell response specific to the spike antigen of SARS-CoV-2 when immunizing BALB/c mice with our next-generation PLACCINE DNA vaccine," added Mr. Tardugno. "Our goal over the next several quarters is to demonstrate the superiority of Celsion’s multicistronic DNA vaccine over current mRNA vaccines with respect to the quality of immune response (higher affinity of neutralizing antibodies, IgG titers and T-cell response) against multiple SARS-CoV-2 variants, longer duration of immune response and a stable product at lower temperatures."

Recent Developments

GEN-1 Immunotherapy

Interim Data Reported on the OVATION 2 Study. Interim clinical data from the first 36 patients who have undergone interval debulking surgery are as follows:

●20 patients were treated with GEN-1 at a dose of 100 mg/m² plus NACT, with 16 out of 20 patients (80%) having R0 resections.
●16 patients were treated with NACT only, with 9 out of 16 patients (56%) having R0 resections.
●When combining these results with the surgical resection rates observed in the Company’s prior Phase Ib dose-escalation trial (the OVATION 1 Study), a population of patients with inclusion criteria identical to the OVATION 2 Study, the data reflect the strong dose-dependent efficacy of adding GEN-1 to NACT.

●The objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria for the 16 patients treated with NACT only were comparable, as expected, to the 20 patients treated with GEN-1 at a dose of 100 mg/m² plus NACT, with both groups demonstrating an approximate 80% ORR.
Publication of OVATION 1 Study in the Journal of Clinical Cancer Research. In July 2021, the Company announced the publication of data from its Phase 1b OVATION 1 Study with GEN-1 in combination with NACT in patients with advanced ovarian cancer in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). The study, authored by Premel H. Thaker, M.D. et al. and titled "GEN-1 in Combination with Neoadjuvant Chemotherapy for Patients with Advanced Epithelial Ovarian Cancer: A Phase I Dose-Escalation Study," is available here. Dr. Thaker, Professor of Gynecologic Oncology and Director of Gynecologic Oncology Clinical Research at the Washington University School of Medicine in St. Louis, is the study chair for the OVATION program.

The OVATION 1 Study enrolled 18 patients with newly diagnosed stage IIIC and IV epithelial ovarian cancer in a standard 3+3 dose-escalation design testing four GEN-1 doses (36 mg/m2, 47 mg/m2, 61 mg/m2 and 79 mg/m2) in combination with NACT (carboplatin-paclitaxel). There were 15 patients evaluable for safety, and 14 underwent interval debulking and were evaluable for RECIST.

As previously reported, there were no dose-limiting toxicities. As shown in the chart below, in the two highest doses of GEN-1 the objective response rate was 100% and the R0 resection rate was 88%. Newly published data show the CRS, which was analyzed in this paper for the first time, was 50% in the two highest doses of GEN-1, compared with 28% from a major publication evaluating CRS scoring.

Clinical Responses: Tumor Response, Surgical Outcome, Pathological Response and Chemotherapy Response Score with NAC/GEN-1 Escalating Doses

Translational Responses: IL-12 and IFN-γ Levels, Response to Immune-Suppressive Agents; Ratio of CD8+ Cells to Immune Suppressive Agents

●A dose-dependent increase in immunostimulatory cytokines IL-12 and its downstream cytokine IFN-γ in ascitic fluid. The anticancer effects of these cytokines are widely recognized in human malignancies.
●The proportion of myeloid dendritic cells in the peritoneal fluid trended higher (3.1-fold) accompanied by a similar 3.0-fold rise in CD8+ cells.
●GEN-1 appeared to reduce four immunosuppressive signals (Foxp3, IDO1, PD-1 and PD-L1) within the tumor microenvironment, a trend not seen with NAC therapy alone.
●GEN-1 appeared to stimulate the body’s immune system through the production of CD4 and CD8 cells.
●GEN-1 gene therapy was associated with an apparent increase in the cytotoxic state of T cells within the tumor microenvironment as indicated by the increases in the ratios of CD8+/CD4+ and CD8+/Treg cells. Indeed, higher CD8+/CD4+ T cell and CD8+/Treg ratios are considered prognostic for prolonged survival.

Vaccine Initiative

Vaccine Advisory Board Expanded. In July 2021, the Company announced the addition of Dan H. Barouch, M.D., Ph.D. and Luke D. Handke, Ph.D. to its Vaccine Advisory Board (VAB). They joined Britt A. Glaunsinger, Ph.D. and Xinzhen Yang, M.D., Ph.D. on the VAB, which was formed in February 2021.

Dr. Barouch is the principal investigator at the Barouch Laboratory, Director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and William Bosworth Castle Professor of Medicine at Harvard Medical School. In addition, he is a key participant in the Bill & Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery, the National Institutes of Health Martin Delaney HIV-1 Cure Collaboratory and the Ragon Institute of MGH, MIT and Harvard. Dr. Barouch and his team were instrumental in developing the vector, a variant of an adenovirus called Ad26, that was used to make single-dose vaccines for HIV, tuberculosis and Zika, and ultimately, in conjunction with Johnson & Johnson researchers, SARS-CoV-2. He has authored numerous peer-reviewed articles.

Dr. Handke is a highly skilled molecular biologist and microbiologist with a decade of pharmaceutical industry experience including nine years with Pfizer’s Vaccine Research and Early Development Unit. At Pfizer he served as molecular biology lead on an early phase viral vaccine program and was the lead reviewer of data sources and literature citations for licensure application for the Trumenba meningococcal group B vaccine in the U.S. and in Europe. He began his career in vaccine research at Wyeth. He is co-author and co-inventor on various patent applications for a protein-based RSV vaccine and a SARS-CoV-2 detection assay and authored 10 peer-reviewed publications including six as first author. Dr. Handke is currently a Senior Scientist at the University of Nebraska Medical Center in Omaha. In addition to serving on the VAB, Dr. Handke will provide consulting services to Celsion in connection with its vaccine-development program, which involves DNA-based vectors in combination with proprietary non-viral cellular delivery agents. He also will advise Celsion as it advances this program into human clinical studies.

Results from In Vivo Studies with PLACCINE DNA Vaccine Platform Indicate Immune Response Against SARS-Cov-2. In September 2021, the Company announced results from preclinical in vivo studies showing production of antibodies and cytotoxic T-cell response specific to the spike antigen of SARS-CoV-2 when immunizing BALB/c mice with the Company’s next-generation PLACCINE DNA vaccine platform. Moreover, the antibodies to SARS-CoV-2 spike antigen prevented the infection of cultured cells in a viral neutralization assay. The production of antibodies predicts the ability of PLACCINE to protect against SARS-CoV-2 exposure, and the elicitation of cytotoxic T-cell response shows the vaccine’s potential to eradicate cells infected with SARS-CoV-2. These findings demonstrate the potential immunogenicity of Celsion’s PLACCINE DNA vaccine, which is hypothesized to provide broad-spectrum protection and resistance against variants by incorporating multiple viral antigens, to improve vaccine stability at storage temperatures of 4oC and above, and to facilitate cheaper and easier manufacturing. Celsion reported these data at the International Vaccines Conference in October 2021.

Agreement with Hainan Poly Pharm to Manufacture Celsion’s DNA-based Vaccine. In September 2021, the Company announced an amendment to its existing contract manufacturing agreement with Hainan Poly Pharm Co. Ltd., a generics manufacturer dedicated to providing therapeutic-value products and services to patients and customers around the world, to include development work for the Company’s investigational DNA-based COVID-19 vaccine. Under the terms of the amended agreement, Poly Pharm will manufacture clinical batches and, if approved for use, will also manufacture commercial batches for Celsion’s vaccine based on its TheraPlas technology. Poly Pharm is experienced with chemistry, manufacturing and controls (CMC), process development and good manufacturing processes (cGMP), including process optimization and manufacturing services to help customers advance new drug development projects. Its sites and pharmaceutical compounds have been approved by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), China’s National Medical Products Administration (NMPA) and the World Health Organization (WHO).

Oral Presentation on Celsion’s Ongoing Work with DNA-based Vaccines at International Vaccines Congress. In October 2021, the Company announced that Khursheed Anwer, Ph.D., executive vice president and chief science officer, presented at the International Vaccines Congress . Dr. Anwer’s presentation was titled "Immunogenicity of DNA Vaccines based on Multicistronic Vectors and Synthetic DNA Delivery Systems" and can be viewed here. Dr. Anwer discussed ongoing proof-of-concept studies in SARS-CoV-2 with the Company’s DNA-based vaccine approach utilizing its PLACCINE platform. PLACCINE, Celsion’s proprietary design for DNA vectors, encompasses molecular elements designed to improve the immune response by targeting multiple antigens of a pathogen or multiple mutants of the same antigen. Dr. Anwer also reviewed the PLACCINE technology and the production of a family of DNA vaccine vectors expressing one or more SARS-CoV-2 surface antigens as a proof-of-concept target, verified vector composition and demonstrated expression of the encoded genes.

Corporate Developments

Presentations at Three Healthcare Investment Conferences. Celsion management made presentations at the following investment conferences in October:

●Chardan’s 5th Annual Genetic Medicines Conference. Michael H. Tardugno, Celsion’s chairman, president and chief executive officer, and Khursheed Anwer, Ph.D., Celsion’s chief scientific officer, participated in a fireside chat.
●LD Micro Main Event. Jeffrey W. Church, Celsion’s chief financial officer, presented virtually.
●Alliance Global Partners’ Virtual Healthcare Conference. Mr. Tardugno participated in an oncology focused panel discussion moderated by James Molloy, Research Analyst.

Third Quarter Financial Results

For the quarter ended September 30, 2021, Celsion reported a net loss of $5.4 million ($0.06 per share), compared with a net loss of $8.1 million ($0.24 per share) in the same period of 2020. Operating expenses were $5.2 million in the third quarter of 2021, which represented a $0.9 million (21%) increase from $4.3 million in the same period of 2020.

The Company ended the third quarter of 2021 with $60.6 million in cash, investment securities, restricted cash and accrued interest receivable. Coupled with future sales of unused New Jersey NOL’s, the Company believes it has sufficient capital resources to fund its operations through the end of 2024.

Research and development (R&D) expenses were $2.5 million in the third quarter of 2021, consistent with $2.5 million reported in the third quarter of 2020. Costs associated with the OVATION 2 Study were $0.2 million in each of the third quarters of 2021 and 2020. R&D costs associated with both the development of GEN-1 to support the OVATION 2 Study and the development of the PLACCINE DNA technology platform increased to $1.1 million in the third quarter of 2021, compared with $0.7 million in the same period of 2020. Clinical development costs for the Phase III OPTIMA Study decreased $0.3 million to $0.2 million in the third quarter of 2021, compared with $0.5 million in the third quarter of 2020, due to the discontinuation of this 556-patient trial in the first quarter of 2021. Other costs related to clinical supplies and regulatory support for the Company’s clinical development programs decreased to $1.0 million in the third quarter of 2021 from $1.1 million in the third quarter of 2020, largely driven by higher manufacturing costs for GEN-1 clinical supplies for the Phase II portion of the OVATION 2 Study, offset by lower regulatory and manufacturing costs related to the OPTIMA Study.

General and administrative expenses were $2.7 million in the third quarter of 2021, compared with $1.8 million in the same period of 2020. The $0.9 million increase was primarily attributable to higher non-cash stock-compensation expense ($0.2 million), an increase in legal and professional fees ($0.6 million) and an increase in Directors’ and Officers’ insurance premiums ($0.1 million).

Non-operating expenses of $0.3 million in the third quarter of 2021 decreased from $3.9 million in the third quarter of 2020 due to (i) a non-cash charge of $1.1 million for the change in valuation of the earn-out milestone liability for the GEN-1 ovarian product candidate recognized in the third quarter of 2020 compared with a $0.3 million non-cash charge recognized in the current quarter; (ii) a non-cash charge of $2.4 million related to the impairment of certain in-process research and development assets related to the development of the Company’s glioblastoma multiforme (GBM) cancer product candidate in the third quarter of 2020; and (ii) lower interest expense of $0.4 million on the Company’s debt facilities in the current quarter, compared with the comparable prior year period. In June 2021, the Company entered into a new $10.0 million loan facility with SVB, with a portion of the proceeds used to retire all outstanding indebtedness under the Company’s venture debt facility entered in late June 2018 with Horizon Technology Finance Corporation.

Nine Month Financial Results

For the nine months ended September 30, 2021, the Company reported a net loss of $16.5 million ($0.21 per share), compared with a net loss of $18.5 million ($0.62 per share) in the same period of 2020. Operating expenses were $15.9 million during the first nine months of 2021, which represented a $1.8 million (13%) increase from $14.1 million in the same period of 2020.

Net cash used for operating activities was $11.1 million in the first nine months of 2021, compared with $11.9 million in the same period in 2020. This was in line with the Company’s projected cash utilization for 2021 of approximately $17 million, or an average of approximately $4.25 million per quarter. Cash provided by financing activities of $54.8 million during the first nine months of 2021 was derived from equity offerings in January 2021 and April 2021, the $10 million loan facility with SVB in June 2021 and the sale of the Company’s unused New Jersey NOLs in May 2021.

Research and development expenses decreased $0.9 million to $7.6 million in the first nine months of 2021 from $8.5 million in the comparable prior-year period. Costs associated with the OVATION 2 Study increased to $1.0 million in the first nine months of 2021 compared to $0.7 million in the same period of 2020. The Company initiated enrollment in the Phase 2 portion of the study during the third quarter of 2020. R&D costs associated with the development of GEN-1 to support the OVATION 2 Study as well as development of the PLACCINE DNA technology platform increased to $3.1 million in the first nine months of 2021, compared with $2.3 million in the comparable 2020 period. Costs for the Phase III OPTIMA Study decreased $1.2 million to $0.6 million in the first nine months of 2021, compared with $1.8 million in the first nine months of 2020, due to the discontinuation of this trial in the first quarter of 2021. Other costs related to clinical supplies and regulatory support for the Company’s clinical development programs decreased $0.8 million to $2.9 million in the first nine months of 2021, compared with the same prior-year period due to lower regulatory and manufacturing costs for the discontinued Phase III OPTIMA Study.

General and administrative expenses were $8.3 million in the first nine months of 2021, compared with $5.5 million in the same period of 2020. The $2.8 million increase was primarily attributable to higher non-cash stock-compensation expense ($1.0 million), an increase in legal and professional fees ($1.4 million) and an increase in Directors’ and Officers’ insurance premiums ($0.2 million).

Other expenses during the first nine months of 2021 included a non-cash charge of $0.3 million for the change in valuation of the earn-out milestone liability for the GEN-1 ovarian product candidate, compared with a non-cash charge of $1.4 million during the comparable prior-year period and a non-cash charge of $2.4 million related to the impairment of certain in-process research and development assets related to the development of the Company’s GBM cancer product candidate in the third quarter of 2020. In connection with the Company’s venture debt facilities, the Company incurred interest expense of $0.5 million during the first nine months of 2021, compared with $1.1 million during the same period in 2020. In June 2021, the Company entered into a new $10.0 million loan facility with SVB, with a portion of the proceeds used to retire all outstanding indebtedness under the Company’s venture debt facility with Horizon Technology Finance Corporation.

Conference Call

The Company will host a conference call to provide a business update, discuss its third quarter 2021 financial results and answer questions at 11:00 a.m. ET today. To participate in the call, please dial 1-800-353-6461(Toll-Free/North America) or +1-334-323-0501 (International/Toll) and ask for the Celsion Corporation Third Quarter 2021 Earnings Call (Conference Code: 4154518). The call will also be broadcast live on the internet at www.celsion.com. The call will be archived for replay through December 1, 2021. The replay can be accessed at +1-719-457-0820 or 888-203-1112 using Conference ID: 4154518. An audio replay will also be available on the Company’s website, www.celsion.com, for 90 days after 2:00 p.m. ET on November 15, 2021.

On November 15, 2021 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported its financial results for the third quarter ended September 30, 2021 (Press release, Syndax, NOV 15, 2021, View Source [SID1234595600]). In addition, the Company provided a clinical and business update.

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"We are thrilled to announce that the pivotal Phase 2 portion of AUGMENT-101, examining SNDX-5613 across three distinct patient populations, is open and enrolling following a productive meeting with the U.S. Food and Drug Administration (FDA)," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "Supported by a growing body of data, we firmly believe that SNDX-5613 is ideally positioned to be first to market and serve as a meaningful intervention for patients with mutant nucleophosmin (NPM1c) and mixed lineage leukemia rearranged (MLLr) acute leukemias who are deeply in need of effective therapies. We look forward to presenting updated data from the Phase 1 portion of the AUGMENT-101 trial, including updated durability of CR/CRh responses, during an oral session at the upcoming 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting."

"We were also pleased to recently announce our partnership with Incyte for the development and commercialization of axatilimab. This agreement represents a key step forward in our strategy to expand and maximize the program across multiple lines of treatment in chronic graft-versus-host disease (cGVHD) as well as additional fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF), where the monocyte-macrophage lineage plays a vital role. As we continue to execute on advancing the program, we look forward to sharing updated data from our Phase 1/2 trial of axatilimab in cGVHD during an oral session at the ASH (Free ASH Whitepaper) Annual Meeting next month."

Recent Pipeline Progress and Anticipated Milestones

SNDX-5613

The Phase 2 portion of AUGMENT-101 is currently enrolling patients with NPM1c mutant and MLLr relapsed/refractory (R/R) acute leukemias. A total of 64 adult and up to 10 pediatric patients will be enrolled across each of the following three distinct trial populations: patients with NPM1 mutant acute myeloid leukemia (AML), patients with MLLr AML, and patients with MLLr acute lymphocytic leukemia. Discussions with the FDA have confirmed that AUGMENT-101 may potentially serve as the basis for regulatory filings in each of the three distinct trials. The primary endpoint for each of the three trials will be efficacy as measured by complete remission rate (complete response [CR] + CR with partial hematologic recovery rate [CRh]), with key secondary endpoints including duration of response and overall survival.
In November 2021, the Company announced that updated data from the Phase 1 portion of the ongoing AUGMENT-101 trial will be featured during an oral session at the 63rd ASH (Free ASH Whitepaper) Annual Meeting being held December 11-14, 2021. Data included in the abstract demonstrated robust clinical activity with durable responses and no discontinuations due to treatment-related adverse events. The oral presentation will include updated Phase 1 data from additional patients as of a more recent cutoff date, as well as further details on durability and CR/CRh rate by mutational status.
The Company reported plans to initiate a new trial to assess the anti-leukemic efficacy of SNDX-5613 in NPM1 or MLLr patients with measurable residual disease (MRD) progression following initial treatment. The trial will be conducted as part of the Australian Leukemia and Lymphoma Group (ALLG) INTERCEPT Master Clinical Trial, a collaborative clinical trial investigating novel therapies to target early relapse and clonal evolution as pre-emptive therapy in AML. SNDX-5613 is the first menin inhibitor to be included in the INTERCEPT AML Master Clinical Trial. The Company expects ALLG to initiate the trial in the first half of 2022.
In August 2021, the Company announced plans to initiate two additional trials to assess the safety, tolerability, and preliminary anti-leukemic efficacy of SNDX-5613 in combination with venetoclax and azacitidine as part of the Leukemia & Lymphoma Society’s Beat AML Master Clinical Trial, and in combination with chemotherapy in patients with R/R NPM1 or MLLr acute leukemias in the AUGMENT-102 trial. The Company expects both trials to initiate in the first half of 2022.
Axatilimab

In November 2021, the Company announced that updated data from its Phase 1/2 trial of axatilimab in patients with cGVHD will be featured during an oral session at the 63rd ASH (Free ASH Whitepaper) Annual Meeting. Data included in the abstract demonstrated broad efficacy and tolerability for axatilimab in patients with relapsed or refractory cGVHD. The oral presentation will include additional follow up on all patients enrolled.
Enrollment is ongoing in the Company’s global pivotal Phase 2 AGAVE-201 trial of axatilimab in patients with cGVHD, with topline data expected in 2023. The trial will evaluate the safety and efficacy of three doses and schedules of axatilimab. The primary endpoint will assess objective response rate based on the 2014 NIH consensus criteria for cGVHD, with key secondary endpoints including duration of response and improvement in modified Lee Symptom Scale score.
In September 2021, Syndax and Incyte announced that they entered into an exclusive worldwide collaboration and license agreement to develop and commercialize axatilimab. Syndax and Incyte are seeking to develop axatilimab as a backbone therapy for patients with cGVHD as well as in additional immune-mediated diseases where CSF-1R-dependent monocytes and macrophages are believed to contribute to organ fibrosis. In addition to the ongoing global pivotal Phase 2 AGAVE-201 trial of axatilimab monotherapy in patients with cGVHD, the companies also plan to initiate additional trials of axatilimab in patients with cGVHD in 2022, including a Phase 2 trial in combination with a JAK inhibitor in patients with steroid-refractory cGVHD. Beyond cGVHD, Syndax plans to commence a Phase 2 proof of concept trial of axatilimab mid next year in patients with IPF, a serious, life-limiting orphan disease for which axatilimab may represent a much-needed treatment option with a novel mechanism of action.
Corporate Updates

In September 2021, Syndax announced the expansion of its Board of Directors to nine members with the appointment of Martin H. Huber, M.D. Dr. Huber has over 20 years of academic, biotechnology, and pharmaceutical drug development experience, currently serving as the President of Research and Development (R&D) and Chief Medical Officer of Xilio Therapeutics, Inc.
Third Quarter 2021 Financial Results

As of September 30, 2021, Syndax had cash, cash equivalents and short-term investments of $229.7 million and 52.2 million shares and share equivalents issued and outstanding. This includes 3.3 million pre-funded warrants.

Third quarter 2021 R&D expenses increased to $25.6 million from $14.4 million for the prior year period. The increase was primarily due to increased clinical trial activities and CMC activities for both SNDX-5613 and axatilimab.

General and administrative expenses for the third quarter 2021 increased to $6.8 million from $5.8 million for the prior year period. The increase is primarily due to increased professional fees.

For the three months ended September 30, 2021, Syndax reported a net loss attributable to common stockholders of $20.6 million or $0.40 per share compared to $20.4 million or $0.46 per share for the prior year period.

Financial Update and Guidance

For the full year of 2021, R&D expenses are expected to be $90 to $100 million, and total operating expenses are expected to be $110 to $120 million.

Conference Call and Webcast

In connection with the earnings release, Syndax’s management team will host a conference call and live audio webcast at 4:30 p.m. ET today, Monday, November 15, 2021.

The live audio webcast and accompanying slides may be accessed through the Events & Presentations page in the Investors section of the Company’s website at www.syndax.com. Alternatively, the conference call may be accessed through the following:

For those unable to participate in the conference call or webcast, a replay will be available on the Investors section of the Company’s website, www.syndax.com.

On November 15, 2021 Instil Bio, Inc. ("Instil") (Nasdaq: TIL), a clinical-stage biopharmaceutical company focused on developing tumor infiltrating lymphocyte, or TIL, therapies for the treatment of patients with cancer, reported poster presentations demonstrating pre-clinical data of the CoStimulatory Antigen Receptor (CoStAR) platform at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2021), held from November 10-14, 2021 (Press release, Instil Bio, NOV 15, 2021, View Source [SID1234595616]). Instil also presented a Trials-in-Progress poster detailing DELTA-1, the ongoing Phase 2 study of ITIL-168 in advanced melanoma.

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Pre-clinical data of the anti-FOLR1 CoStAR construct utilized in ITIL-306, Instil’s first genetically-engineered CoStAR-TIL product candidate, was shown in Poster 198. The results demonstrated that CoStAR broadly enhances effector function of T cells including cytolytic activity, cytokine secretion and proliferation of T cells. CoStAR did not stimulate T cells on its own, but only increased T-cell function in the presence of signals activating both the tumor-reactive TCR and the CoStAR molecule. Additionally, data were presented that showed CoStAR was transduced at high efficiency (greater than 40%) into primary ovarian cancer TILs and effector function of CoStAR-TIL was increased over untransduced TILs when cocultured with autologous tumor cells.

The proprietary CoStAR platform utilizes intracellular CD28 and CD40 domains to deliver novel synergistic costimulatory activity to T cells. Poster 199 showcased enhanced activity of T cells engineered with dual CD28/CD40-containing CoStARs, with greater proliferation, enhanced effector function, and a superior cytokine secretion profile compared to a CD28-only CoStAR. Importantly, CoStAR-expressing T cells proliferated exponentially after exposure to tumor antigen, even in the absence of exogenous interleukin (IL)-2, a key required growth factor for T cells in vitro.

"These data further support our excitement for the CoStAR platform, which addresses a major challenge for solid tumor cell therapy: the lack of effective costimulation within the tumor microenvironment," said Mark Dudley, Ph.D., Head of Research at Instil. "The optimized intracellular signaling domains of our CoStAR platform include CD28 and CD40, which demonstrate superior performance over CoStARs containing only CD28."

"With the encouraging preclinical data presented at SITC (Free SITC Whitepaper), we are optimistic that CoStAR may be able to enhance the activity of TILs in patients with cancer and may eliminate the need for high doses of post-infusion IL-2, which is a frequent cause of toxicity in unmodified TIL therapy," said Zachary Roberts, M.D. Ph.D., Chief Medical Officer of Instil Bio. "We continue to look forward to the upcoming Phase 1 first-in-human study of ITIL-306 which we expect to initiate in the first half of 2022."

The company also presented a trial-in-progress poster for DELTA-1, the ongoing Phase 2 study of ITIL-168 in advanced melanoma (Poster 544).

Details of the poster presentations are as follows:

Title: Costimulatory antigen receptor (CoStAR): a novel platform that enhances the activity of TILs
Authors: Sukumaran S, et al.
Poster/Abstract Number: 198 / DOI: 10.1136/jitc-2021-SITC2021.198

Title: Potent T cell costimulation mediated by a novel costimulatory antigen receptor (CoStAR) with dual CD28/CD40 signaling domains to improve adoptive cell therapies
Authors: Sykorova M, et al.
Poster/Abstract Number: 199 / DOI: 10.1136/jitc-2021-SITC2021.199

Title: A global, multicenter phase 2 study of ITIL-168, an unrestricted autologous TIL cell therapy, in adult patients with advanced cutaneous melanoma
Authors: Gastman B, et al.
Poster/Abstract Number: 544 / DOI: 10.1136/jitc-2021-SITC2021.544

The posters are available on the publications section of the Instil Bio website: www.instilbio.com/publications.

About CoStAR

CoStAR (Co-Stimulatory Antigen Receptor) is a novel platform technology used to create a new class of genetically engineered TIL therapies. These modified TILs rely on their native, patient-specific T cell receptors, or TCRs, for detection of tumor-specific antigens, with significantly enhanced effector function when the CoStAR molecule is simultaneously bound to its target in the tumor microenvironment. Submission of the IND for ITIL-306, Instil’s lead CoStAR-TIL product candidate which binds FOLR1 (Folate Receptor Alpha), is anticipated for the first half of 2022.

About ITIL-168

ITIL-168 is an investigational, autologous cell therapy made from tumor infiltrating lymphocytes, or TILs. Made from each patient’s digested and cryopreserved tumor, ITIL-168 is a TIL cell therapy manufactured to offer an unrestricted T cell receptor (TCR) repertoire. Instil’s proprietary, optimized, and scalable manufacturing process has been designed to capture and preserve the maximum diversity of each patient’s TILs. By collecting the patient’s tumor and immediately processing and then cryopreserving it, our process offers significant scheduling flexibility for patients and physicians at the time of both tumor resection and TIL treatment. In addition to DELTA-1, Instil plans to investigate ITIL-168 in additional solid tumor indications in Phase 1 clinical trials beginning in 2022.

About DELTA-1

DELTA-1 is a global, multicenter Phase 2 clinical trial of ITIL-168 in adult patients with advanced melanoma. Using an open-label, single-arm design, the main study cohort will evaluate the efficacy and safety of ITIL-168, when administered after a 5-day course of lymphodepleting chemotherapy and followed by up to 8 doses of high-dose interleukin-2 (IL-2), in patients whose cancer has progressed following a PD-1 inhibitor and, if positive for a BRAF-activating mutation, a BRAF inhibitor. Approximately 80 subjects are planned for enrollment and treatment in Cohort 1. Cohort 2 is anticipated to enroll approximately 25 subjects and is designed to evaluate the efficacy and safety of the regimen in patients who required discontinuation of PD-1 inhibitor(s) due to unacceptable toxicity, regardless of best overall disease response. Cohort 3 is also anticipated to enroll approximately 25 subjects and will evaluate efficacy and safety in patients whose best ongoing response to PD-1 inhibitor(s) is stable disease. Patients in Cohorts 2 and 3 whose cancer expresses a BRAF-activating mutation will be required to have experienced disease progression following BRAF inhibitor therapy. The primary endpoint of DELTA-1 is the objective response rate (ORR) according to RECIST v1.1 as assessed by independent central review. Secondary endpoints include disease control rate, duration of response, progression-free survival, overall survival, and safety.

On November 15, 2021 Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, reported the publication of a scientific paper in the peer-reviewed international scientific journal, ACS Pharmacology & Translational Science (Press release, Oryzon, NOV 15, 2021, View Source [SID1234595630]). The article reports a comprehensive comparison of iadademstat, the first LSD1 inhibitor to be developed in the clinic, with most of the LSD1 inhibitors in development.

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The manuscript, entitled "Comprehensive in Vitro Characterization of the LSD1 Small Molecule Inhibitor Class in Oncology", compares iadademstat with four LSD1 inhibitors in clinical development in oncology and with five commonly used compounds used in the academia as tool LSD1 inhibitors. Results show that iadademstat is consistently the most active compound across diverse cancer cell lines, that its capability to bind the target is superior, specially at low concentrations, and that the disruption of the transcriptional complexes implicated in the oncogenic programs is more efficacious in the case of iadademstat.

Dr. Jordi Xaus, Oryzon’s CSO, commented: "This set of head-to-head controlled comparisons have shown that iadademstat is clearly the most potent and selective LSD1 inhibitor among all tested clinical molecules. This correlates with the need for lower doses in the clinic, which greatly reduces the potential for idiosyncratic toxicity. A relevant result in this study is that at lower concentrations iadademstat is, by far, the most efficacious in binding LSD1. This may have clinical relevance in solid, dense and poorly vascularized tumors, where the access of drugs to tumoral cells is often an issue".

The paper has been published in the journal ACS Pharmacology & Translational Science as part of the special issue Epigenetics 2022 and is already accessible on-line. The paper can be accessed here: View Source

On November 15, 2021 BioAtla, Inc. (Nasdaq: BCAB), a global clinical-stage biotechnology company focused on the development of Conditionally Active Biologic (CAB) antibody therapeutics, reported financial results for the third quarter of 2021 and provided an update on its clinical progress and business (Press release, BioAtla, NOV 15, 2021, View Source [SID1234595646]).

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"BioAtla continues to advance the progress of the potentially registration-enabling Phase 2 clinical trials for our two lead CAB product candidates as well as our other preclinical and pipeline programs. The increase in our financial resources in the third quarter through our equity placement provides the funding into the first half of 2024 to develop these key assets and the several additional ADC and bispecific CAB candidates in our development pipeline," stated Jay M. Short, Ph.D., Chairman, Chief Executive Officer and co-founder of BioAtla, Inc. "We are aggressively advancing all of our clinical programs and are on track for a sarcoma Phase 2 interim data read out by year-end for BA3011, CAB-AXL-ADC. Additionally, a clinical trial for CAB-CTLA-4 is expected to be initiated by the end of the year," added Scott Smith, President of BioAtla.

Advancing clinical trials for lead candidates
Mecbotamab Vedotin (BA3011)
We are developing BA3011, CAB-AXL-ADC, a conditionally and reversibly active antibody drug conjugate targeting the receptor tyrosine kinase AXL, as a potential therapeutic for multiple solid tumor types, including soft tissue and bone sarcoma, non-small cell lung cancer (NSCLC) and ovarian cancer, with other potential indications in the future. The Office of Orphan Drug Products (OODP) at FDA granted Orphan Drug Designation to BA3011 for the treatment of soft tissue sarcoma, and Phase 1 results in sarcoma patients were presented at the recent Connective Tissue Oncology Society (CTOS) 2021 Annual Meeting. BA3011 was generally well tolerated in this refractory sarcoma population. Few patients discontinued due to an adverse event (2 patients out of 26 or 7.7%). No clinically meaningful on-target toxicity to normal AXL-expressing tissue was observed. Dose-limiting toxicities were limited to monomethyl auristatin E (MMAE) conjugate-associated toxicity at the highest dose tested, including reversible neutropenia.The degree of AXL tumor membrane expression correlated with response to treatment. Of the seven sarcoma patients who had an AXL tumor membrane percent score of greater than or equal to 70, four of these obtained a confirmed partial response, including patients with leiomyosarcoma, undifferentiated pleomorphic sarcoma, and Ewing sarcoma. Prolonged response to therapy was observed in this ongoing study with the duration of response ranging from 33 to more than 60 weeks. Overall, mecbotamab vedotin may have a favorable benefit-risk profile, and importantly this is one of the few studies with a putative biomarker which is not only highly expressed in sarcomas, but also may help select patients across multiple sarcoma subtypes who may benefit from therapy. In the ongoing potentially registration-enabling sarcoma Phase 2 study, patients are enrolled for therapy by prescreening for AXL expression. We also are conducting a Phase 2 study (BA3011-002) in AXL high NSCLC patients who have previously progressed on PD-1/L1, EGFR, or ALK inhibitor therapy. We currently expect to have enrolled more than 70 patients by year end in our sarcoma Phase 2 trial in the U.S. Interim analyses in the sarcoma and NSCLC trials are anticipated this year and in early 2022, respectively. In addition, a multi-center investigator-initiated Phase 2 clinical trial of BA3011 in combination with a PD-1 inhibitor in patients with platinum-resistant ovarian cancer is expected to begin enrollment by year end.

BA3021 (Ozuriftamab Vedotin)
BA3021, CAB-ROR2-ADC, is a conditionally and reversibly active antibody drug conjugate directed against ROR2, a receptor tyrosine kinase that is overexpressed across many different solid tumors including lung, head and neck, melanoma and breast. We are developing BA3021 as a potential therapeutic for multiple solid tumor types, including NSCLC, melanoma, squamous cell cancer of the head and neck (SCCHN) and ovarian cancer. Based on Phase 1 data we believe BA3021 has broad potential as a cancer therapy for patients with advanced solid tumors that have previously progressed on a PD-1 inhibitor. We are enrolling a Phase 2 trial of BA3021 monotherapy or in combination with a PD-1 inhibitor in patients with ROR2 high melanoma who have previously progressed on PD-1/L1 inhibitor and patients with ROR2 high NSCLC who have previously progressed on PD-1/L1, EGFR or ALK inhibitor therapy. A Phase 2 study in patients with ROR2 high SCCHN is anticipated to enroll in early 2022. In addition, a multi-center investigator-initiated Phase 2 clinical trial of BA3021 in combination with a PD-1 inhibitor in patients with platinum-resistant ovarian cancer is expected to begin enrollment by year end.

BA3071
BA3071, is a CAB anti-CTLA-4 antibody that is being developed as an immuno-oncology agent with the goal of delivering efficacy comparable to the approved anti-CTLA-4 antibody, ipilimumab, but with lower toxicities due to the CAB’s tumor microenvironment-restricted activation. The development of BA3071 is the subject of a 2019 Global Co-Development and Collaboration Agreement between BioAtla and BeiGene, Ltd. Like BA3011, BA3021 and our other CAB candidates, BA3071 is designed to be conditionally and reversibly activated in the tumor microenvironment via the Protein-associated Chemical Switch or PaCS mechanism discovered by BioAtla scientists. This proprietary system enables reduction of systemic toxicity and potentially enables safer combination therapies, such as with anti-PD-1 antibody checkpoint inhibitors in the case of BA3071. BA3071 is being developed as a potential therapeutic for multiple solid tumor indications, including renal cell carcinoma, NSCLC, small cell lung cancer, hepatocellular carcinoma, melanoma, bladder cancer, gastric cancer and cervical cancer. We are currently in advanced discussions with BeiGene regarding the allocation of roles and responsibilities for global development and commercialization of BA3071 under our Global Co-Development and Collaboration Agreement with BeiGene. As part of these ongoing discussions, BeiGene is planning to initiate the transfer of the IND for BA3071 to BioAtla and BioAtla anticipates initiating the Phase I trial for BA3071 during 2021, with dosing commencing in the first half of 2022.

Plans to advance development of several bispecific CAB candidates
We have also leveraged our CAB technology to develop bispecific antibodies, which bind both a tumor-specific antigen and a T cell receptor (CD3) using CAB antigen-binding domains. With this design, bispecific antibodies can induce potent T cell responses against tumors expressing the tumor target antigen. We have shown in preclinical experiments that our CAB bispecific molecules meet or exceed the activity of conventional bispecifics and reduce systemic activation of potentially severe immune responses. We are conducting IND-enabling studies for two CAB bispecific antibody product candidates, EpCAM/CD3 and B7-H3/CD3, and presently plan to file INDs in mid-2022 and by year end 2022, respectively. We also are evaluating additional candidates including EGFR and Nectin-4 for CAB CD3 bispecific modalities. Nectin-4 is also progressing as a CAB ADC candidate. Overall, we are advancing multiple pre-clinical assets with the potential to submit up to four US INDs over the next 18 months for our CAB bispecific or ADC molecules.

Sheri Lydick joins to lead commercial strategy
BioAtla is building its capabilities to plan for and execute the commercial launches of its CAB portfolio of product candidates. A key element of this strategy is the recent hiring of Sheri Lydick as the company’s Senior Vice President, Commercial Strategy. Ms. Lydick will be leading commercial strategy, which includes long-range portfolio planning, assessing strategic business opportunities and delivering on these plans. Ms. Lydick has more than 20 years of leadership and commercialization experience in the biotechnology and pharmaceutical industry. In her most recent role at Bristol-Meyers Squibb Company, Ms. Lydick was responsible for building the sales and marketing teams and leading the commercial launch of Zeposia across multiple therapeutic areas (multiple sclerosis and ulcerative colitis). In her twelve years (2007-2019) at Celgene her leadership role expanded from Director of Global Marketing for the Inflammation and Immunology (I&I) Franchise to Executive Director, US Rheumatology Lead, to Vice President, US Commercial Lead for Zeposia. Among her accomplishments, she was instrumental in building Celgene’s Inflammation and Immunology franchise and led the planning and launch of the multi-billion dollar drug Otezla. BioAtla president Scott Smith commented, "Sheri has deep experience and success in global commercial marketing and sales and in building and leading multidisciplinary teams. We are excited for her to bring that expertise to BioAtla."

Third quarter 2021 financial results
Cash and cash equivalents as of September 30, 2021 were $269.9 million. We expect current cash and cash equivalents will be sufficient to fund planned operations into the first half of 2024. In September 2021, we executed a private placement of common stock yielding gross proceeds of $75.0 million before deducting placement agent fees and other offering expenses. The investors included both current and new institutional investors.

Research and development (R&D) expenses were $16.6 million for the quarter ended September 30, 2021 compared to $4.9 million for the same quarter in 2020. We expect our R&D expenses to increase substantially for the foreseeable future as we continue to invest in R&D activities to advance our product candidates, and our clinical programs and expand our product candidate pipeline.

General and administrative (G&A) expenses were $7.1 million for the quarter ended September 30, 2021 compared to $3.3 million for the same quarter in 2020. We expect our G&A expenses to increase as a result of operating as a public company. In addition, we expect our intellectual property expenses to increase as we expand our intellectual property portfolio.

Net loss for the third quarter ended September 30, 2021 was $22.9 million compared to a net loss of $11.6 million for the same quarter in 2020. Net cash used in operating activities for the first nine months of 2021 was $41.3 million compared to net cash used in operating activities of $22.3 million for the same period in 2020.