On April 8, 2022 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, reported that it will present additional positive immunogenicity and clinical data on TG4050, its individualized neoantigen cancer vaccine (Press release, Transgene, APR 8, 2022, View Source [SID1234611721]). TG4050 is currently being evaluated in two ongoing multicenter Phase I trials in patients with ovarian cancer and head and neck cancer. In a poster presentation, Transgene will discuss how these new data further demonstrate the ability of this neoantigen cancer vaccine to induce strong immune responses, targeting patient-specific mutations, that are expected to translate into clinical benefit for patients.

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These results will be presented during a late-breaking poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) meeting on April 12, 2022, in New Orleans, Louisiana, USA.

New immune cell response data confirm the ability of this individualized vaccine to effectively prime the immune system

Transgene is presenting a comprehensive set of immunological data. Circulating immune cells quantification (in particular monocytes, DC, NK cells, subcells of CD8, CD4, Treg) and expression of immune checkpoints (ICOS and PD1) suggest that the vaccine is able to effectively induce innate and adaptive immune responses in patients.

All evaluable patients developed a robust T-cell responses against multiple targeted neoantigens (median of 10 positive responses per patient). T-cell responses were observed for class I and class II epitopes, they consisted of de novo responses and amplifications of preexisting responses.

New clinical data obtained from patients treated with TG4050 provide a positive update on the two ongoing trials

In the head and neck trial, patients have been randomized to immediatly receive vaccination with TG4050 (early treatment arm, arm A) or at relapse (delayed vaccination arm, arm B). All patients randomized to arm A (n=7) are stable as of mid-March 2022. In arm B (n=6), two patients have recently experienced relapse.

In the ovarian trial (n=4), one patient treated after an elevation of CA-125 experienced a normalization of CA-125 without clinical progression for 9 months until death from an unrelated chronic illness. Another patient was treated upon onset of radiological evidence of relapse and was stable for 11.4 months.

To date, the vaccine has been well tolerated and no related Serious Adverse Events have been reported across the two studies.

In both clinical studies, enrollment and patient dosing are progressing in line with our expectations. Overall, Transgene plans to treat 13 patients in the ovarian cancer trial and 30 patients in the head and neck trial.

Poster title: Phase I trials of personalized cancer vaccine TG4050 in surgically treated high-risk head and neck squamous cell carcinoma (HNSCC) and relapsing ovarian cancer (OvC) patients

·Session title: Phase I Clinical Trials 2

· Poster and abstract number: CT182

· Date, time, location: Tuesday, April 12, 2022, 9:00 AM – 12:30 PM CDT, Board 7, Section 33

· Authors: M. Block, JP Delord, C. Ottensmeier, C. Le Tourneau, A. Lalanne, O. Lantz, K. Knutson, G. Lacoste, A. Tavernaro, M. Brandely, N. Silvestre, B. Grellier, Y. Yamashita, O. Kousuke, N. Yamagata, E. Quemeneur, K. Bendjama

The abstract and the poster can be accessed on the AACR (Free AACR Whitepaper) and Transgene websites.

First positive preliminary clinical data generated in the first patients treated with TG4050 were announced in November 2021 and can be found here.

Transgene is also presenting preclinical data obtained with BT-001 at the AACR (Free AACR Whitepaper) meeting. BT-001 is an Invir.IO based oncolytic virus, encoding a Treg-depleting human recombinant anti-CTLA-4 antibody generated by BioInvent and the human GM-CSF cytokine.

Poster title: "Comprehensive preclinical studies of BT-001: an oncolytic vaccinia virus armed with Treg‑depleting @CTLA4 and GM-CSF"

Poster and abstract number: 3567
More information can be found here.

The abstract and the poster can be accessed on the AACR (Free AACR Whitepaper) and Transgene websites.

About the clinical trials

TG4050 is being evaluated in two Phase I clinical trials for patients with ovarian cancer (NCT03839524) and HPV-negative head and neck cancers (NCT04183166).

In a first Phase I trial, TG4050 is being administered to patients with HPV-negative head and neck cancer. A personalized treatment is created for each patient after they complete surgery and while they receive an adjuvant therapy. Half of the participants receive their vaccine immediately after they complete their adjuvant treatment. The other half is given TG4050 as an additional treatment at the time of recurrence of the disease. This randomized study is evaluating the treatment benefits of TG4050 in patients who have a high risk of relapse. Up to 30 patients will receive TG4050 in France, in the UK and in the USA. The principal investigator of the trial is Prof. Christian Ottensmeier, MD, PhD, Consultant Medical Oncologist at the Clatterbridge Cancer Centre and Professor of Immuno-Oncology at the University of Liverpool. In France, the clinical trial is being conducted at Institut Curie, Paris by Prof. Christophe Le Tourneau, MD, PhD, Head of the Department of Drug Development and Innovation (D3i), and at the IUCT-Oncopole, Toulouse by Prof. Jean-Pierre Delord. In the USA, the trial is being led by Dr. Yujie Zhao, MD, PhD, at the Mayo Clinic. Endpoints of the trial include safety, feasibility and biological activity of the therapeutic vaccine.

In parallel, a Phase I clinical trial of TG4050 is enrolling patients with ovarian cancer. This second trial is including patients at the time of asymptomatic relapse after surgery and first-line chemotherapy. Dr. Matthew Block, MD, PhD, Consultant Medical Oncology, Consultant Immunology and Associate Professor of Oncology at the Mayo Clinic (USA) is the principal investigator of the trial; in France, the trial is being conducted by Prof. Le Tourneau, MD, PhD, at Institut Curie and by Dr. Alexandra Martinez, MD, Associate Head of Surgical Department, at IUCT-Oncopole. Endpoints of the trial include safety, feasibility and biological activity of the therapeutic vaccine.

First positive preliminary clinical data generated in the first patients treated with TG4050 were announced in November 2021. More information here or in this video here.

About myvac

myvac is a viral vector (MVA – Modified Vaccinia Ankara) based, individualized immunotherapy platform that has been developed by Transgene to target solid tumors. myvac-derived products are designed to stimulate the patient’s immune system, recognize and destroy tumors using the patient’s own cancer specific genetic mutations. Transgene has set up an innovative network that combines bioengineering, digital transformation, established vectorization know-how and unique manufacturing capabilities. Transgene has been awarded "Investment for the Future" funding from Bpifrance for the development of its platform myvac. TG4050 is the first myvac-derived product being evaluated in clinical trials.

About TG4050

TG4050 is an individualized immunotherapy being developed for solid tumors that is based on Transgene’s myvac technology and powered by NEC’s longstanding artificial intelligence (AI) expertise. This virus-based therapeutic vaccine encodes neoantigens (patient-specific mutations) identified and selected by NEC’s Neoantigen Prediction System. The prediction system is based on more than two decades of expertise in AI and has been trained on proprietary data allowing it to accurately prioritize and select the most immunogenic sequences.

TG4050 is designed to stimulate the immune system of patients in order to induce a T-cell response that is able to recognize and destroy tumor cells based on their own neoantigens. This individualized immunotherapy is developed and produced for each patient.

On April 8, 2022 Sutro Biopharma, Inc. ("Sutro" or the "Company") (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation cancer therapeutics, reported new nonclinical data for its folate receptor alpha (FolRα) targeting antibody-drug conjugate (ADC) STRO-002, in an e-poster session, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, being held virtually and in New Orleans from April 8-13, 2022 (Press release, Sutro Biopharma, APR 8, 2022, View Source [SID1234611720]).

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STRO-002 is an ADC designed to target FolRα, which is currently in Phase 1 clinical trials for the treatment of ovarian and endometrial cancers. In the e-poster session presented at AACR (Free AACR Whitepaper), studies in vitro demonstrate STRO-002’s ability to induce hallmarks of immunogenic cell death. Studies in vivo show that pre-administration of STRO-002 to FolRα-expressing tumor cells confers anti-tumor immunity as demonstrated by both rejection of the primary tumor and significant protection after a tumor re-challenge. Further, in vivo induction of immunogenic cell death extended to a complementary anti-tumor mechanism in combination with a checkpoint inhibitor (avelumab) in re-challenged animals. Additionally, when STRO-002 was administered in combination with an anti-VEGF antibody (bevacizumab), the tumor growth was significantly inhibited.

Nonclinical studies using endometrial and non-small cell lung cancer (NSCLC) patient derived xenograft models with diverse levels of FolRα expression demonstrated robust STRO-002 activity, with the degree of efficacy correlating with FolRα levels. Similar activity was also seen in cells with moderate to low levels of FolRα expression. In the NSCLC model, a STRO-002 dose of 10 mg/ml resulted in significant and long-term responses.

"These nonclinical data provide insight into STRO-002’s immunogenic cell death properties and reveal its potential to elicit host immune system engagement and potentiate efficacy in a targeted and dependent manner," said Trevor Hallam, Ph.D., President of Research and Chief Scientific Officer at Sutro. "The potent cytotoxic and immune stimulatory properties of STRO-002 through immunogenic cell death may also enhance activity in indications that are thought to have lower levels of FolRα such as in non-small cell lung cancer and endometrial cancers."

The data is being presented as an e-poster at the AACR (Free AACR Whitepaper) Annual Meeting, with details as follows:

The poster is accessible through the Clinical/Scientific Presentation and Publication Highlights page of the News section of the company’s website at www.sutrobio.com.

On April 8, 2022 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported that a poster presentation featuring preclinical data from its GD2 SADA construct will be presented at the AACR (Free AACR Whitepaper) Annual Meeting 2022, which takes place in New Orleans, Louisiana from April 8-13, 2022 (Press release, Y-mAbs Therapeutics, APR 8, 2022, View Source [SID1234611719]).

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Pre-clinical models have shown that the tetramerizing function of the SADA domain appears to be important to the binding activity and anti-tumor effect of GD2 SADA. Data confirms that the SADA domain seems to increase tumor antigen binding, uptake and persistence in tumor tissue, and markedly improves anti-tumor responses in pre-clinical models.

The SADA technology was licensed by the Company from Memorial Sloan Kettering ("MSK") and the Massachusetts Institute of Technology. Researchers at MSK developed the SADA technology for radioimmunotherapy, which is exclusively licensed by MSK to Y-mAbs. MSK has institutional financial interests in the technology.

On April 8, 2022 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates," or "MTEM" or "the Company"), a clinical-stage biopharmaceutical company focused on the discovery and development of proprietary targeted biologic therapeutics, engineered toxin bodies (ETBs), reported that it will host a webinar on a unique approach to immuno-oncology for solid tumors on Wednesday, April 13, 2022 at 8:00 am Eastern Time (Press release, Molecular Templates, APR 8, 2022, View Source [SID1234611718]).

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The webinar will feature a presentation from medical expert David Spigel, MD, of the Sarah Cannon Research Institute, who will discuss Molecular Templates’ program, MT-6402 (targeting PD-L1), and the implications of the Phase 1 data as it relates to treating patients with a variety of PD-L1-expressing solid tumors. MT-6402 is the first of the Company’s 3rd generation ETBs to enter the clinic. It is designed to induce potent anti-tumor effects via PD-L1 targeting through mechanisms including Shiga-like Toxin A ribosomal inactivation and CMV antigen-seeding technology, both of which may overcome the limitations of approved checkpoint inhibitors.

The Molecular Templates’ management team will provide a brief company update.

A live question and answer session will follow the formal presentations. To register for the event, please click here.

David Spigel, MD joined Sarah Cannon Research Institute in 2003 and is its chief scientific officer. He oversees all scientific aspects of Sarah Cannon’s clinical trial program, working with the research physician leaders to ensure the best new agents and studies are available to patients. He serves as a primary contact for the pharma and biotech partners as well as the strategic site physicians with whom Sarah Cannon conducts cancer research.

Dr. Spigel received his bachelor’s degree from Tulane University in New Orleans and medical degree from The University of Tennessee in Memphis. After completing an internal medicine and chief residency at Indiana University Medical Center, he completed a fellowship in hematology and oncology at The Dana-Farber Cancer Institute in Boston. He is board certified in medical oncology. Additionally, he is a partner with Tennessee Oncology, PLLC.

On April 8, 2022 Advaxis, Inc. (OTCQX: ADXS), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products reported the publication of results of their KEYNOTE-46 Phase 1/2 open-label, double-arm trial of ADXS-PSA with KEYTRUDA (pembrolizumab) in patients with metastatic, castration-resistant prostate cancer (mCRPC) (Press release, Advaxis, APR 8, 2022, View Source [SID1234611717]). The paper, titled "ADXS31­142 Immunotherapy ± Pembrolizumab Treatment for Metastatic Castration-Resistant Prostate Cancer: Open-Label Phase I/II KEYNOTE-046 Study," has been published online in The Oncologist. The article can be found online here.

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The KEYNOTE-46 trial was conducted in conjunction with Merck (known as MSD outside the U.S. and Canada) and evaluated ADXS-PSA, one of Advaxis’ Listeria monocytogenes (Lm)-based immunotherapies, alone and in combination with KEYTRUDA, Merck’s anti-PD-1 therapy.

"The published clinical and immunogenicity data demonstrate that ADXS-PSA in combination with KEYTRUDA has the potential to provide meaningful increases in median overall survival in patients with advanced, metastatic, castration-resistant prostate cancer," said Kenneth A. Berlin, President and Chief Executive Officer of Advaxis. "Furthermore, these demonstrated improvements in survival in an advanced patient population encourage us to continue researching and developing the next generation of Lm-immunotherapies such as our off-the shelf, multineoantigen drug construct, ADXS-504, currently being studied in biochemically recurrent prostate cancer. ADXS-504 is a novel treatment alternative for these earlier stage prostate cancer patients, that has the potential to delay androgen blockade therapy initiation, improve quality of life and increase life expectancy."

As of the January 28, 2020, data cut off, 50 patients with mCRPC were enrolled with evaluable responses in Advaxis’ Ph 1/2 trial of ADXS-PSA alone and ADXS-PSA in combination with KEYTRUDA. The median overall survival (OS) in 13 patients treated with ADXS-PSA alone was 7.8 months (95%CI: 4.4-18.5) with progression free survival (PFS) of 2.2 months (95%CI: 0.8–7.4). The median OS on ADXS-PSA combined with KEYTRUDA was 33.7 months (95%CI: 15.4-NR), while median PFS was 5.4 months (95%CI: 2.3–7.9; n=37). 56.8% (21/37) of patients on combination therapy and 30.8% (4/13) on monotherapy showed stable disease. Robust response was also observed with the combination therapy in patients with prior docetaxel treatment and visceral metastasis. In addition, patients in the combination arm who had prior docetaxel treatment (n=20; 17 of whom had also received 1 or 2 next generation hormonal agent (NGHA) therapies) had an OS of 16.0 months (95%CI: 6.4-34.6), while patients with prior visceral metastasis (n=11; 10 of whom had prior docetaxel and 9 whom had received 1-2 prior NGHA therapies) had an OS of 16.4 months (95%CI: 4.0-NE). Of note, 36 of the 37 patients in the combination arm were tested for microsatellite instability and were all found to be Microsatellite Stable (MSS).

The combination of ADXS-PSA and KEYTRUDA increased T-cell expansion compared to ADXS-PSA alone, suggesting broader immune stimulation. In addition, contraction of T-cell clones was observed in the combination group, which suggests that T-cell clones with lower avidity for PSA (and other prostate-related antigens) were reduced in favor of high-avidity T cells under PD-1 blockade. The combination arm also showed antigen spreading with antigen-specific T-cell responses documented against other relevant prostate cancer antigens.

Naomi B Haas, MD, Director of the Prostate and Kidney Cancer Program and Professor of Medicine at University of Pennsylvania Hospital, and senior author of this publication, said, "Altogether these data are encouraging given the prolonged survival observed in patients in the combination therapy arm regardless of prior therapy with docetaxel, NGHAs or presence of visceral metastasis. It is interesting to see increases in median overall survival to 16.4 months in patients with measurable disease/visceral metastasis as compared to historical data of ≤9.5 months with pembrolizumab alone in this population." She added, "Furthermore, one patient who completed the 2-year study-treatment with ADXS-PSA in combination with KEYTRUDA moved on to a compassionate use protocol and remained with stable disease for yet another 22 months while on combination treatment. These outcomes, delivered with a generally safe and well-tolerated treatment regimen, may warrant additional evaluation of ADXS-PSA in combination with KEYTRUDA or of new generation Lm-immunotherapies in prostate cancer."

The combined therapy was safe and well tolerated in this heavily pretreated population. All patients had more than one treatment-related adverse event, mostly transient Grade 1-2 chills/rigors, fever, hypotension, nausea and fatigue, with no additive toxicity on the combination therapy.

About KEYNOTE-046
KEYNOTE-046 (NCT02325557) was an open-label, multicenter, dose-determining, safety and tolerability Phase 1/2 trial of 50 heavily pretreated patients conducted in two parts (Part A and Part B), with a Phase 2 expansion cohort. While the objective of the study was to evaluate ADXS-PSA as a monotherapy (Part A; n=14 [13 treated]) and in combination with KEYTRUDA (Part B; n= 37) in heavily pretreated patients with progressive and refractory mCRPC, the study was not designed to compare the two treatment regimens. Primary endpoints included safety, tolerability and dosing. Secondary endpoints were anti-tumor activity, progression-free survival and overall survival, and exploratory endpoints included associations between biomarkers of immunologic response (serum PSA) with clinical outcomes.