On September 17, 2020 A team led by researchers from Case Western Reserve University School of Medicine and Cleveland Clinic Lerner Research Institute reported that it has secured $10.4 million over five years from the National Institutes of Health/National Cancer Institute to explore at the molecular level the differences in glioblastoma between males and females (Press release, Case Western Reserve University, SEP 17, 2020, View Source [SID1234565273]).

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The researchers will delve into the genetics, epigenetics and cell biology of glioblastoma—the most common and deadliest brain tumor in adults—to better understand the physiologic processes that may lead to more personalized therapies.

The researchers have previously published research showing significant differences between the sexes in glioblastoma incidence, survival and some key molecular pathways. They found that glioblastoma is 60% higher in males than in females. In addition, females have a significant survival advantage over males with a median improved survival rate of up to 10 months. However, while these sex differences are understood, they are not yet considered when treating glioblastoma.

The research team is led by co-principal investigators Justin Lathia of Cleveland Clinic’s Lerner Research Institute and Jill Barnholtz-Sloan of Case Western Reserve University School of Medicine. The team also includes colleagues from Penn State College of Medicine, Washington University School of Medicine in St. Louis and the Translational Genomics Research Institute (TGen).

Glioblastomas are rare—about 3.5-4 per 100,000 in the United States from 2012-16, the most recent data available from the Central Brain Tumor Registry of the United States (CBTRUS). Despite available treatments, glioblastomas have devastating consequences for patients. The median survival time is 12 to 14 months, and only about 5% of patients survive more than five years.

"We have the molecular profiling technology and the computing and analytical strength to lead in this effort to better understand the role of sex differences in cancer, particularly for glioblastoma," said Barnholtz-Sloan, the Sally S. Morley Designated Professor in Brain Tumor Research and associate director of data sciences at the Case Comprehensive Cancer Center, Case Western Reserve School of Medicine. "This next phase of research relies on vast, varied and complex datasets—in animals and humans—and promises to be a game-changer in how we understand the role of sex in tumor formation and disease outcomes. This comprehensive approach has applications to all forms of cancer, as well as other diseases."

"Sex differences are inherent drivers of glioblastoma incidence and survival, and we are taking a multidimensional approach to uncover a better understanding of this differentiation," said Lathia, vice chair of the Department of Cardiovascular and Metabolic Sciences and co-director of the Brain Tumor Research & Therapeutic Development Center of Excellence at Lerner Research Institute, and co-leader of the Molecular Oncology Program at the Case Comprehensive Cancer Center. "We are incorporating data from tumor cells and their surrounding micro-environment, as well as genetic programs responsible for tumor growth, and underlying epigenetic differences that may be responsible for sex differences. We aim to gain a better understanding of how these variables interrelate to better understand disease mechanism, which in turn defines better diagnostics and more personalized therapies for patients."

The multi-disciplinary project involves established investigators with complementary expertise and a strong collaborative history. Along with Lathia and Barnholtz-Sloan, participating institutions and their PIs include:

Washington University School of Medicine in St. Louis: Joshua Rubin
Penn State College of Medicine: James Connor
Translational Genomics Research Institute (TGen): Michael Berens
Three related research projects, undertaken by this collaborative team, will delve into the basic biology and cellular mechanisms that drive sex differences in glioblastoma formation and progression. These related research projects will inform, synergize and depend on each other. Findings from the labs based on their animal models will then be queried against data from human clinical samples across multiple institutions. The vast amount of data generated from these studies requires robust data management and sophisticated data analysis for a comprehensive view of sex differences across these diverse but related inquiries.

Comprehensive findings will inform future clinical research design, the search for targets for new therapeutics, or the use of existing therapeutics that may be applied differently depending on a patient’s sex.

This grant was made by the NIH’s National Cancer Institute. Grant number: 1P01CA245705.

On September 17, 2020 Bio-Techne Corporation (NASDAQ: TECH) and QIAGEN N.V. reported the expansion and extension of a non-exclusive partnership to co-market exosome technology to existing and potential biopharma partners as well as the joint development of new exosome based products (Press release, Bio-Techne, SEP 17, 2020, View Source [SID1234565272]).

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The agreement grants QIAGEN a non-exclusive development license to Bio-Techne’s exosome technology for the development of companion in vitro diagnostic products (CDX-IVD) for existing and potential biopharma partners. Following the agreement, both Bio-Techne and QIAGEN will be actively promoting the use of exosome technology to their respective global biopharma partners. The initial phase of the co-marketing agreement lasts 24 months, with the potential to extend longer upon the fulfillment of certain conditions.

The two companies also announced the extension and expansion of the existing exclusive collaboration and license agreement that was originally in place between Exosome Diagnostics (now a Bio-Techne company) and QIAGEN. The agreement includes leveraging Exosome Diagnostics’ proprietary platforms for biomarker discovery for the joint development of new products and for ongoing marketing activities to promote exosome technologies. The extended collaboration and joint product development agreement ends in 2028 and can be extended if mutually agreed to by both companies.

"QIAGEN is an ideal partner to co-market and co-develop products leveraging our proprietary exosome technology," commented Chuck Kummeth, President and Chief Executive Officer of Bio-Techne. "We are excited to expand our partnership with an established global diagnostics leader and anticipate both companies as well as current and future biopharma partners to benefit from the expanded agreement."

"Bio-Techne’s exosome technology represents a novel diagnostic approach with broad applications that will be especially beneficial to our global pharma partners," said Thierry Bernard, Chief Executive Officer of QIAGEN. "We see numerous applications for this technology and remain enthusiastic on its potential. We look forward to co-marketing this technology and collaborating on innovative companion diagnostic products for our global biopharma partners."

On September 17, 2020 Clovis Oncology, Inc. (NASDAQ: CLVS) reported the data being presented as e-posters at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020 (Press release, Clovis Oncology, SEP 17, 2020, View Source [SID1234565270]). These include initial data from the Phase 1b part of the LIO-1 study of lucitanib in combination with Opdivo, new analyses of data from the pivotal Rubraca ARIEL3 and TRITON2 studies, initial data from the Phase 1b part of the SEASTAR study arm of Rubraca with Trodelvy (sacituzumab govitecan-hziy), and the first presentation of preclinical data for FAP-2286 Clovis’ novel peptide-targeted radionuclide therapy.

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"We are very pleased to present these encouraging initial datasets for our pipeline compounds lucitanib and FAP-2286 today, as well as data further characterizing and confirming the established safety profile of Rubraca in advanced ovarian and prostate cancers, which we believe provides additional, valuable information to physicians and their patients," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We are enthusiastic about the potential of our clinical development programs for each of our three compounds and remain committed to exploring the full depth and breadth of our pipeline to transform the cancer treatment landscape and hopefully improve outcomes for patients."

Data presented today from the Phase 1b part of the Phase 1b/2 LIO-1 study in patients with an advanced solid tumor (n=17) have identified the recommended starting Phase 2 dose of oral lucitanib to be used in combination with Opdivo and have shown promising signs of antitumor activity. The recommended oral starting dose of lucitanib was established as 6 mg once daily, to be given in combination with Opdivo at a fixed dose of 480 mg intravenously (IV) once every 28 days. Across three dose levels studied (6 mg, 8 mg and 10 mg) of oral lucitanib in combination with intravenous (IV) Opdivo at (480 mg once every 28 days), only one dose-limiting toxicity of Grade 3 proteinuria was observed among 17 patients, and there were no apparent differences in treatment-emergent adverse event (TEAE) frequencies between dose levels. In this small patient population, TEAEs were consistent with those expected for lucitanib and Opdivo. Grade 3 TEAEs included hypertension (n=4), diarrhea (n=1), and proteinuria (n=1); treatment-emergent hypertension was otherwise grade 1 or 2 (n=4), and readily managed with close monitoring and early hypertensive therapy. No grade ≥4 adverse events were reported. Given lucitanib’s relatively large inter-patient pharmacokinetic variability, a safety-based dose-titration approach is being used for the Phase 2 part of the study to optimize lucitanib efficacy as well as safety and tolerability. Among the 17 patients treated, 15 were evaluable for RECIST response as of the efficacy cut-off date: these include one patient with a confirmed complete response, one patient with a confirmed partial response, 10 patients have had a best response of stable disease and three patients had progressive disease. As of August 11, 2020, seven of the 17 patients remained on study, including the two responders and five of the patients with stable disease.

"We have completed enrollment in the Phase 1b part of the LIO-1 trial, and have identified a dose of lucitanib to take into Phase 2 combined with nivolumab. The combination showed promising signs of activity in unselected solid tumors in patients with very advanced disease, including one patient with a confirmed complete response," said Dr. Erika Hamilton, Director of the Breast and Gynecologic Research Program, Sarah Cannon Research Institute at Tennessee Oncology. "We were also encouraged by the initial safety profile, in particular as it relates to constitutional side effects, and hope to build on that with our dose-titration approach in the ongoing Phase 2 part of the LIO-1 study. This will provide greater understanding of what this combination may offer for the treatment of patients with gynecological cancers."

In addition to data from the Phase 1b part of the LIO-1 study, a Trials in Progress (TiP) poster describing the study design of the Phase 2 part of LIO-1 was presented. The Phase 2 part of the study is currently enrolling patients to evaluate the efficacy and safety of the lucitanib and Opdivo combination in patients with advanced gynecological solid tumors, including ovarian, endometrial and cervical cancers. As described in the e-poster, a safety-based dose-titration approach is being used for lucitanib dosing to manage tolerability and maintain dose intensity.

Investigators also presented today new safety data analyses from the pivotal Rubraca studies ARIEL3 and pharmacokinetic (PK) analyses of TRITON2, providing additional information to healthcare professionals that can help support their ovarian and prostate cancer patients being treated with Rubraca.

The ARIEL3 data presented in an e-poster reinforce the overall safety profile of Rubraca as a maintenance treatment in patients with recurrent ovarian cancer. After two years of additional follow up for those patients who continued on treatment in the study, the safety profile remains consistent with previous reports, with no new safety signals identified. As of the current safety data cutoff (December 31, 2019), 33 of 372 and 1 of 189 patients in the safety population were still receiving Rubraca or placebo, respectively. Median treatment duration was 8.3 months in the Rubraca arm and 5.5 months in the placebo arm. Prevalence of any-grade nausea declined progressively over the 24-month evaluation period, and prevalence of any-grade anemia/decreased hemoglobin peaked at month 4, decreasing to a plateau after month 8. The first onset of frequently reported TEAEs generally occurred early in treatment (≤45 days). The median duration of the first event of frequently reported TEAEs was generally <60 days.

Population pharmacokinetic (PK) analyses of 199 men with mCRPC receiving Rubraca in the TRITON2 study suggest there is no difference in Rubraca PK in men with mCRPC and women with ovarian cancer based on a comparison to a previously-developed model that used data from 454 women with ovarian cancer treated with Rubraca. The data in men with mCRPC show that differences among patients in the amount of Rubraca in the blood after administration of Rubraca at a dose of 600 mg twice daily did not appear to impact the efficacy of treatment. Also, a higher maximum concentration of Rubraca in the blood was not associated with increased rates of most safety endpoints analyzed, including hematologic adverse events. These PK data and exposure and safety/efficacy correlations using data from the TRITON2 study support the use of Rubraca in eligible mCRPC patients with a starting dose of 600 mg twice daily. TRITON2 served as the pivotal data supporting the May 2020 FDA approval of Rubraca as the first PARP inhibitor for patients with advanced mCRPC associated with a BRCA mutation.

Investigators also presented in an e-poster initial data from the arm of the Phase 1b/2 SEASTAR study evaluating Rubraca in combination with Trodelvy in patients with advanced solid tumors (n=6). Data from the Phase 1b part of the study suggest encouraging initial antitumor activity for the novel combination, including patients with prior PARP inhibitor exposure and without a deleterious homologous recombination repair gene mutation. Despite early toxicities, including dose-limiting neutropenia in two of the three patients in the higher dose cohort, all six patients continued treatment for at least 12 weeks, with side effects effectively managed with dose modification and/or growth factor support. One patient remained on treatment as of the August 11, 2020 data cut-off date. All patients had a best response of stable disease or better, including three patients with a confirmed partial response (all three had been previously treated with a PARP inhibitor).

And finally, the first data from a preclinical evaluation of FAP-2286, Clovis’ novel peptide-targeted radionuclide therapy to fibroblast activation protein (FAP) were presented in an e-poster. The data show that FAP-2286 potently and selectively binds FAP. FAP is highly expressed in cancer-associated fibroblasts (CAFs) present in the tumor microenvironment of most epithelial cancers and, in some cancers, its expression has also been observed in the tumor cells. Compelling anti-tumor activity was observed with 177Lu-FAP-2286 (Lutetium-177 conjugated to FAP-2286 for therapeutic use) in FAP-expressing tumor models. Clovis Oncology plans to submit two Investigational New Drug (IND) applications in late 2020 for use of this novel radionuclide therapy as an imaging and treatment agent, respectively, and the Company has planned clinical studies in a broad spectrum of FAP-positive cancers.

Each of Clovis Oncology’s e-posters described are available online at www.clovisoncology.com/pipeline/scientific-presentations.

About Rubraca (rucaparib)

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.

Rubraca is an unlicensed medical product outside of the U.S. and Europe

Rubraca (rucaparib) European Union (EU) authorized use and Important Safety Information

Rubraca is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

Rubraca is indicated as monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with ≥2 prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Efficacy of Rubraca as treatment for relapsed or progressive epithelial ovarian cancer (EOC), fallopian tube cancer (FTC), or primary peritoneal cancer (PPC) has not been investigated in patients who have received prior treatment with a PARP inhibitor. Therefore, use in this patient population is not recommended.

Summary warnings and precautions:

Hematological toxicity

During treatment with Rubraca, events of myelosuppression (anemia, neutropenia, thrombocytopenia) may be observed and are typically first observed after 8–10 weeks of treatment with Rubraca. These reactions are manageable with routine medical treatment and/or dose adjustment for more severe cases. Complete blood count testing prior to starting treatment with Rubraca, and monthly thereafter, is advised. Patients should not start Rubraca treatment until they have recovered from hematological toxicities caused by previous chemotherapy (CTCAE grade ≥1).

Supportive care and institutional guidelines should be implemented for the management of low blood counts for the treatment of anemia and neutropenia. Rubraca should be interrupted or dose reduced according to Table 1 (see Posology and Method of Administration [4.2] of the Summary of Product Characteristics [SPC]) and blood counts monitored weekly until recovery. If the levels have not recovered to CTCAE grade 1 or better after 4 weeks, the patient should be referred to a hematologist for further investigations.

MDS/AML

MDS/AML, including cases with fatal outcome, have been reported in patients who received Rubraca. The duration of therapy with Rubraca in patients who developed MDS/AML varied from less than 1 month to approximately 28 months.

If MDS/AML is suspected, the patient should be referred to a hematologist for further investigations, including bone marrow analysis and blood sampling for cytogenetics. If, following investigation for prolonged hematological toxicity, MDS/AML is confirmed, Rubraca should be discontinued.

Photosensitivity

Photosensitivity has been observed in patients treated with Rubraca. Patients should avoid spending time in direct sunlight because they may burn more easily during Rubraca treatment; when outdoors, patients should wear a hat and protective clothing, and use sunscreen and lip balm with sun protection factor of 50 or greater.

Gastrointestinal toxicities

Gastrointestinal toxicities (nausea and vomiting) are frequently reported with Rubraca, and are generally low grade (CTCAE grade 1 or 2), and may be managed with dose reduction (refer to Posology and Method of Administration [4.2], Table 1 of the SPC) or interruption. Antiemetics, such as 5-HT3 antagonists, dexamethasone, aprepitant and fosaprepitant, can be used as treatment for nausea/vomiting and may also be considered for prophylactic (i.e. preventative) use prior to starting Rubraca. It is important to proactively manage these events to avoid prolonged or more severe events of nausea/vomiting which have the potential to lead to complications such as dehydration or hospitalization.

Embryofetal toxicity

Rubraca can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings from animal studies. In an animal reproduction study, administration of Rubraca to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity at exposures below those in patients receiving the recommended human dose of 600 mg twice daily (see Preclinical Safety Data [5.3] of the SPC).

Pregnancy/contraception

Pregnant women should be informed of the potential risk to a fetus. Women of reproductive potential should be advised to use effective contraception during treatment and for 6 months following the last dose of Rubraca (see section 4.6 of the SPC). A pregnancy test before initiating treatment is recommended in women of reproductive potential.

Click here to access the current SPC. Healthcare professionals should report any suspected adverse reactions via their national reporting systems.

Rubraca U.S. FDA Approved Indications

Ovarian Cancer

Rubraca is indicated for the maintenance treatment of adult women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Rubraca is indicated for the treatment of adult women with a deleterious BRCA mutation (germline and/or somatic)-associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies. Select patients for therapy based on an FDA-approved companion diagnostic for Rubraca.

Prostate Cancer

Rubraca is indicated for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Select Important Safety Information

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) occur in patients treated with Rubraca, and are potentially fatal adverse reactions. In 1146 treated patients, MDS/AML occurred in 20 patients (1.7%), including those in long term follow-up. Of these, 8 occurred during treatment or during the 28 day safety follow-up (0.7%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 53 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing regimens and/or other DNA damaging agents.

Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue Rubraca.

Based on its mechanism of action and findings from animal studies, Rubraca can cause fetal harm when administered to a pregnant woman. Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Rubraca. For males on Rubraca treatment who have female partners of reproductive potential or who are pregnant, effective contraception should be used during treatment and for 3 months following the last dose of Rubraca.

Most common adverse reactions in ARIEL3 (≥ 20%; Grade 1-4) were nausea (76%), fatigue/asthenia (73%), abdominal pain/distention (46%), rash (43%), dysgeusia (40%), anemia (39%), AST/ALT elevation (38%), constipation (37%), vomiting (37%), diarrhea (32%), thrombocytopenia (29%), nasopharyngitis/upper respiratory tract infection (29%), stomatitis (28%), decreased appetite (23%), and neutropenia (20%).

Most common adverse reactions in Study 10 and ARIEL2 (≥ 20%; Grade 1-4) were nausea (77%), asthenia/fatigue (77%), vomiting (46%), anemia (44%), constipation (40%), dysgeusia (39%), decreased appetite (39%), diarrhea (34%), abdominal pain (32%), dyspnea (21%), and thrombocytopenia (21%).

Co-administration of rucaparib can increase the systemic exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated. If co-administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of international normalized ratio (INR) monitoring.

Because of the potential for serious adverse reactions in breast-fed children from Rubraca, advise lactating women not to breastfeed during treatment with Rubraca and for 2 weeks after the last dose.

Please click here for full Prescribing Information for Rubraca.

About Lucitanib

Lucitanib is an oral, potent inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3), platelet-derived growth factor receptors alpha and beta (PDFGRα/β) and fibroblast growth factor receptors 1 through 3 (FGFR1-3). Emerging clinical data support the combination of angiogenesis inhibitors and immunotherapy to increase effectiveness in multiple cancer indications. Angiogenic factors, such as vascular endothelial growth factor (VEGF), are frequently up-regulated in tumors and create an immunosuppressive tumor microenvironment. Use of antiangiogenic drugs may reverse this immunosuppression and augment response to immunotherapy.

Lucitanib is an unlicensed medical product.

About FAP-2286

FAP-2286 is a preclinical candidate discovered by 3B Pharmaceuticals under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein alpha (FAP). FAP is highly expressed in many epithelial cancers, including more than 90 percent of breast, lung, colorectal and pancreatic carcinomas. Clovis Oncology is planning to submit an investigational new drug application (IND) for FAP-2286 in the second half of 2020 and conduct the global clinical trials. Clovis Oncology holds U.S. and global rights, excluding Europe.

FAP-2286 is an unlicensed medical product.

On September 17, 2020 LAVA Therapeutics, a biotech company pioneering the development of bispecific antibodies to engage gamma-delta T cells for cancer therapies, reported the closing of an oversubscribed $83 million (€71 million) Series C financing to fund the advancement of its pipeline and platform (Press release, Lava Therapeutics, SEP 17, 2020, View Source [SID1234565255]). The financing was co-led by new investors Novo Ventures, the venture arm of Novo Holdings, and Sanofi Ventures, and included additional new investors Redmile Group, LLC, Ysios Capital and BB Pureos Bioventures. In addition, current investors Versant, Gilde Healthcare and MRL Ventures Fund, LLC participated significantly in the round.

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As part of the transaction, Nanna Lüneborg, partner at Novo Ventures, Laia Crespo, EU head of investments at Sanofi Ventures, and Joël Jean-Mairet, managing partner and co-founder of Ysios, joined LAVA as members of the board of directors.

"We are grateful to have attracted a high-quality syndicate of new investors complementing strong continued support of our existing investors. This financing provides meaningful capital to advance our bispecific gamma-delta T cell engager portfolio into multiple proof-of-concept clinical trials expected to start in 2021 for the treatment of solid tumors and hematologic malignancies," said Stephen Hurly, chief executive officer of LAVA Therapeutics. "We believe our targeted approach, leveraging the unique features of gamma9-delta2 T cells with innovative bispecific antibodies, will deliver novel T cell-based therapies offering advantages over today’s oncology treatments. In addition to the funding raised, the appointments of Nanna, Laia and Joël to our board further strengthen our team, and we look forward to benefiting from their insights and industry expertise."

Gamma-delta T cells are the natural surveillance cells of the immune system, continuously patrolling the human body for the identification and targeting of tumor cells. These cells bridge the innate with the adaptive immune system and are a largely untapped opportunity in cancer treatment. LAVA’s bispecific gamma-delta T cell engager platform is harnessing the unique properties of these T cells creating a revolutionary truly tumor-targeted immunotherapy to improve outcomes for cancer patients.

"LAVA’s bispecific antibody approach to targeting and engaging gamma-delta T cells has the potential to transform the treatment of a wide range of cancers," said Dr. Lüneborg. "We are impressed by the preclinical data generated by LAVA to date, which validate the company’s platform and support their transition into a clinical-stage organization. The team is highly experienced in drug development, and I look forward to working with them."

"Gamma-delta T cells are an emerging field and an incredibly exciting area in oncology. Bispecific antibodies able to directly engage this type of cells offer the potential to significantly impact patients across the globe in these diseases with high morbidity and mortality," said Dr. Crespo.

On September 16, 2020 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, reported its financial results for the six-month period ended June 30, 2020, and provides an update on progress of its portfolio (Press release, Transgene, SEP 16, 2020, View Source [SID1234621821]).

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Philippe Archinard, Chairman and Chief Executive Officer of Transgene, commented:

"I would like to thank the teams at Transgene for their remarkable job in advancing all our clinical and preclinical projects in an environment that has been severely disrupted by the Covid-19 pandemic. During the period we delivered positive Phase 1b/2 results with TG4001, which have given us the confidence to progress the clinical development of this therapeutic vaccine against HPV-induced cancers. We intend to provide more detail on these positive Phase 1b/2 study results in the coming months. Our oncolytic virus TG6002 showed positive initial data in a Phase 1 trial, indicating that it induces the production of a chemotherapy agent in the tumor.

These promising results confirm the safety of TG6002 when given intravenously and are highly supportive of the new generations of oncolytic viruses that we are developing based on our exciting Invir.IO platform. Patient inclusion continues in line with expectations in the first trials of the individualized immunotherapy TG4050, which has been generated from our myvac platform. The myvac platform and the launch of these trials earlier this year exemplify our technological leadership in individualized immunotherapies. The data which were presented at the AACR (Free AACR Whitepaper) congress in June highlighted the power of NEC’s artificial intelligence and the integration of the first block chain solution into the myvac production process. In parallel, we successfully produced the first clinical batches of TG4050. The collaboration with AstraZeneca continues with the delivery of new oncolytic viruses. Finally, by selling part of approximately 40% of the stake in Tasly BioPharmaceuticals for $22.2 million, Transgene has the cash resources to fund its activities until 2022." Page 2/9 Promising initial data for TG4001 The analysis of the efficacy data from the Phase 1b/2 trial combining TG4001 with avelumab in HPV16-positive recurrent and/or metastatic malignancies showed a promising clinical activity in the overall study population (34 evaluable patients).

In addition, Transgene identified a selection criterion corresponding to patients showing particularly encouraging clinical activity. For more than 50% of these patients, the disease had not progressed at 12 weeks, compared to an expected median progression-free survival (PFS) of 8 weeks for this population with current treatment regimens or with immune checkpoint inhibitors in monotherapy. Responses are durable in most of the responder patients. Transgene is currently completing translational analyses. Patient follow-up is still ongoing. Complete data will be presented at an upcoming scientific conference. Transgene intends to pursue the development of TG4001 and is actively working on the preparation of a confirmatory clinical study. Advanced technological leadership with the myvac platform Transgene is developing the therapeutic vaccine TG4050, together with NEC. This individualized cancer vaccine is based on the myvac platform and integrates NEC’s artificial intelligence capabilities. The first Phase 1 clinical trials assessing TG4050 in patients with ovarian and head and neck cancers started in January 2020 in Europe and in the United States. NEC is financing 50% of these studies.

The Company has set up an in-house production unit dedicated to the manufacturing of the individualized clinical batches of TG4050 needed for each patient. This unit is operational and complies with good manufacturing practice (GMP) norms. The manufacturing process and unit have been validated and the first clinical batches have been produced.

The myvac platform is being actively promoted as it exemplifies Transgene’s technological leadership in individualized immunotherapies.
✓ Data validating the vaccine design principle and underlining the accuracy of the artificial intelligence used to personalize TG4050 were presented at the AACR (Free AACR Whitepaper) congress (June 2020).
✓ Transgene has implemented the first block chain solution dedicated to the traceability of personalized treatment in clinical trials. This cloud-based solution monitors and orchestrates all of the processes related to the design and manufacturing of Transgene’s individualized therapeutic vaccine TG4050.
✓ Other innovative approaches were integrated into the myvac approach and will be detailed in the coming months. The initial translational data of TG6002 highlight the potential of the Invir.IO platform Initial data from the Phase 1 trial confirm the good tolerability of TG6002 in humans and demonstrate that this Vaccinia Virus, which is the viral backbone on which the Invir.IO platform is based, can reach the tumor and replicate within these cancer cells when administered intravenously. BT-001 is the first oncolytic virus from the Invir.IO platform. A first-in-human trial is being prepared; the trial protocol has been filed in France and in Belgium. Promising preclinical results for BT-001 were presented at the AACR (Free AACR Whitepaper) annual congress (June 2020). The collaboration with AstraZeneca continues with the development of new innovative oncolytic viruses.

AstraZeneca can exercise an option to further develop each of these novel drug candidates. Page 3/9 Summary of key ongoing clinical trials TG4001 + Bavencio (avelumab) Phase 1b/2 Targets: HPV16 E6 and E7 oncoproteins Advanced HPV-positive cancers including oropharyngeal head and neck cancer – 2 nd line
✓ Clinical collaboration with Merck KGaA and Pfizer, for the supply of avelumab
✓ Very promising results; patient follow-up is ongoing  Detailed results will be presented at an upcoming scientific conference  Transgene intends to launch a larger, controlled, confirmatory trial myvac TG4050 Phase 1 Targets: tumor neoantigens
✓ Data demonstrating the high accuracy of AI-based neoantigen prediction technology used to design TG4050 were presented at AACR (Free AACR Whitepaper) Ovarian cancer – after surgery and first-line chemotherapy ✓ Trial authorized in the United States and in France
✓ First patient enrolled in January 2020 – inclusions progressing in line with forecast  First scientific communication in 2021 TG4050 Phase 1 HPV-negative head and neck cancer – after surgery and adjuvant therapy ✓ Trial authorized in the United Kingdom and in France
✓ First patient enrolled in January 2020 – inclusions progressing in line with forecast  First scientific communication in 2021 TG6002 Phase 1/2a Payload: FCU1 for the local production of a 5-FU chemotherapy Gastro-intestinal cancer (colorectal cancer for Phase 2) – Intravenous (IV) administration
Multicenter trial ongoing in Belgium, France and Spain
✓ First findings confirm that 5-FU is produced in the tumor  Dose escalation is ongoing in the Phase 1 part, testing additional dose levels TG6002 Phase 1/2a Colorectal cancer with liver metastasis – Intrahepatic artery (IHA) administration ✓ Multicenter trial authorized in the United Kingdom
✓ First patient treated in February 2020; enrollment resuming in September 2020 after pausing due to Covid-19  First observations in 2021 Invir.IO BT-001 Phase 1/2 Payload: anti-CTLA4 antibody and GM-CSF cytokine Solid tumors ✓ Collaboration with BioInvent
✓ First clinical trial applications submitted (France and Belgium) ✓ Presentation of very encouraging preclinical results at AACR (Free AACR Whitepaper) 2020  Approval from health authorities expected before the end of 2020 Key Financials The Board of Directors of Transgene met on September 16, 2020 and approved the financial statements for the six-month period ended June 30, 2020.

The Statutory Auditors have conducted a limited review of the interim consolidated financial statements. The half-year financial report is available on Transgene’s website, View Source Page 4/9 Key elements of the income statement (in thousands of euros) June 30, 2020 June 30, 2019 Operating revenues 5,731 4,909 Research and development expenses (13,831) (14,668) General and administrative expenses (3,297) (3,572) Other expenses-(141) Operating expenses (17,128) (18,381) Operating income/(loss) (11,397) (13,472) Financial income/(loss) 9,183 (1,870) Net income/(loss) (2,214) (15,342) Operating revenues amounted to €5.7 million for the first six months of 2020 compared to €4.9 million for the same period in 2019.

• In 2019, the Company entered into a collaboration agreement with AstraZeneca with exclusive licensing options to co-develop oncolytic immunotherapies derived from the Invir.IO platform. As a result, in the first half of 2019 Transgene received €8.9 million (US$10 million) in fees for access to its platform. This initial payment is recognized as revenue based on the stage of completion of the related activities. Over the period, the income recognized under this collaboration agreement was €2.2 million (€0.7 million in the first half of 2019). Of this amount €1.8 million reflects recognition of the initial payment for work done during the period and €0.4 million for the achievement of certain preclinical milestones.

• The research tax credit amounted to €2.9 million for the first half of 2020, compared to €3.1 million for the first half of 2019. Research and Development (R&D) expenses amounted to €13.8 million in the first half of 2020 compared to €14.7 million for the same period in 2019. External expenses for clinical projects decreased to €3.0 million from €4.7 million in the first half of 2019. This decrease is mainly due to a reduction in subcontracted clinical batch production expenses in the first half of 2020 compared to the same period in 2019. General and administrative expenses amounted to €3.3 million for the first half of 2020 compared to €3.6 million for the same period in 2019. Net interest income amounted to a gain of €9.2 million in the first half of 2020 compared to an expense of €1.9 million for the same period in 2019. This change is mainly due to the increase in the fair value of Tasly Biopharmaceuticals shares: in July 2020, the sale of the shares was carried out at a higher price than the acquisition price in July 2018. This sale price was applied to all the shares held. As a consequence, the net comprehensive loss amounted to €2.2 million for the first half of 2020 compared to a loss of €15.3 million for the same period in 2019. As of June 30, 2020, the Company’s cash, cash equivalents and other financial assets amounted to €33.2 million versus €43.3 million as of December 31, 2019. Transgene’s cash burn amounted to €10.1 million in the first half of 2020, compared with €4.1 million for the same period in 2019.

Transgene intends to reimburse the €10 million bank loan from the European Investment Bank in advance of its June 2021 maturity. The Company confirms its financial visibility until 2022. Page 5/9 Partial sale of the stake in Tasly BioPharmaceuticals On August 4, 2020, Transgene announced the receipt of $22.2 million (€19 million) following the sale to a Chinese investment fund of part of its minority stake in Tasly BioPharmaceuticals. This transaction involved the sale of 10.3 million shares of Tasly BioPharmaceuticals (38% of the shares held by Transgene). Following this share sale, Transgene holds 17.1 million shares in Tasly BioPharmaceuticals, equivalent to 1.58% of the Chinese company’s capital. Transgene’s remaining shareholding in Tasly BioPharmaceuticals is valued at approximately $36.9 million based on the price of the current share sale.

At the end of August 2020, Tasly BioPharmaceuticals filed its IPO documentation with the Science and Technology Innovation Board (STIB) of the Shanghai Stock Exchange. Succession of the Chairman and Chief Executive Officer planned at the end of 2020 Philippe Archinard, Chairman and Chief Executive Officer of Transgene, has informed the Board of Directors of his intention to leave his position at the end of 2020 to take up new responsibilities within Institut Mérieux. The Board has acknowledged his decision and proposes that his successor be Hedi Ben Brahim, who has been a Board member of Transgene since May 2019. This decision will be approved at the Board meeting scheduled on December 3, 2020. Philippe Archinard will remain a Board Member of Transgene thereafter.