On July 22, 2020 ERC-USA, a clinical-stage biopharmaceutical company developing immunotherapies for the treatment of cancer, reported that NYU Winthrop Hospital (NYU) has agreed to treat one of its recurrent, refractory glioblastoma multiforme (GBM) patients with ERC’s lead therapy, ERC1671, under federal and state Right-to-Try laws (RTT) (Press release, Epitopoietic Research, JUL 22, 2020, View Source [SID1234562256]).

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The expansion of ERC’s RTT program makes its unique immuno-oncology GBM treatment, ERC1671, available to a wider number of patients who have exhausted all other treatment options. NYU joins the University of California, Irvine Medical Center and John Theurer Cancer Center Hackensack, NJ in treating recurrent, refractory GBM patients with ERC1671 under RTT. GBM is the most common and aggressive form of brain cancer and patients with this recurrent, refractory disease have very few options.

ERC1671 has demonstrated a clinically meaningful survival benefit among treated patients with minimal toxicity in phase 2 clinical trials. In June, ERC announced that it had submitted its Marketing Authorization Application for ERC1671 to the European Medicines Agency for conditional approval.

ERC will shortly publish a summary of its RTT experience that will include the total number of patients and median survival data. The Company previously communicated that oncologists are reporting that certain terminal patients treated with ERC1671 under RTT are experiencing unprecedented regressions of their disease. Normally, regression of recurrent glioblastoma is not experienced. One patient has already demonstrated a remission that is now in its eighteenth month with no sign of recurrence. The durability of these responses is still not known, but to the families of these patients the responses are unexpected and welcome, and they are restoring some normalcy to the lives of these terminal patients and their families.

"We are extremely eager to expand our RTT program to NYU Winthrop Hospital and we are encouraged and excited by the responses we’ve observed so far in RTT patients to ERC1671. As awareness of ERC1671 grows in the neuro-oncology community, we have been experiencing a major increase in requests for treatment under RTT protocols," commented Apostolos Stathopoulos, M.D., Ph.D., president and CEO of ERC Belgium, parent company to ERC-USA.

About ERC 1671

ERC1671 (Gliovac or Sitoiganap) is an advanced immunotherapy based on freshly extracted tumor cells and lysates that stimulates the patient’s immune system to recognize and reject cancer cells. The ERC1671 contains a combination of autologous tumor cells (cells from the patient receiving the treatment), and allogeneic tumor cells, generated from the glioma tumor tissues of three different donor cancer patients, and the lysates of all of these cells. Upon injection, this mixture stimulates the patient’s immune system to mount an immune response against the tumor cells, which may lead to their destruction.

Gliovac/ERC1671 is for patients suffering from a grade IV glioma (glioblastoma multiforme and gliosarcoma) when all other traditional treatments have failed. Further studies will target patients with newly diagnosed glioma with predictive marker indicating, unresponsiveness to Temozolomide chemotherapy (MGMT gene promoter unmethylation).

ERC1671 is currently in randomized, placebo-controlled Phase 2 clinical trials in the United States as part of combination treatment for glioblastoma multiforme and gliosarcoma and its Marketing Authorization Application has been submitted to the European Medicines Agency for conditional approval. The company’s therapeutic approach can be potentially applied to many other types of solid cancers.

ERC is based in Belgium with a cGMP manufacturing plant in the Netherlands and subsidiaries in the U.S.A., Canada, Australia and an international presence through country specific agreements. To learn more, please visit View Source

On July 22, 2020 T3 Pharmaceuticals AG ("T3 Pharma"), a Swiss biotech advancing immuno-oncology with its bacteria-based protein delivery platform, reported the closing of its third financing round, raising over 25M CHF (Press release, T3 Pharmaceuticals, JUL 22, 2020, View Source [SID1234562255]).

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The financing was co-led by existing investors, including the Boehringer Ingelheim Venture Fund (BIVF), Reference Capital SA, Wille Finance AG and private investors, who all participated in the round. This latest financing brings T3 Pharma’s total funding since the launch of the Company in 2015 to 40 million CHF.

T3 Pharma will use the funds primarily to progress its lead candidate, T3P-Y058-739, through clinical studies. The Phase 1/2 clinical study in solid tumors is planned to start in early 2021.

T3P-Y058-739 is the first therapeutic candidate developed using T3 Pharma’s proprietary protein delivery platform. The technology is built on the discovery that the bacterial type III secretion (T3S) system can be repurposed to deliver chosen proteins into eukaryotic cells.1 T3 Pharma’s live bacteria vehicles have been optimised to accumulate and grow selectively at solid tumors, where they produce and deliver the therapeutic protein.

Dr. Simon Ittig, T3 Pharma’s CEO, commented: "This significant financing round comes at a pivotal moment for our company as we leverage the full potential of our proprietary platform and enter the clinic with our lead candidate. We are grateful to our investors for their continued support."

"Our novel approach to deliver bioactive proteins selectively to cancerous cells using live bacteria has the potential to revolutionize treatment of solid tumors," added Dr. Olivier Valdenaire, Chairman of the Board.

Dr. Frank Kalkbrenner, Global Head of BIVF, commented: "Since I joined the Board last year, I have been impressed not only by the technology, but also by the team and the approach they have taken to building T3 Pharma’s innovative, differentiated platform and progressing its lead candidate. It is an endorsement of the quality of the science and the team that another financing round has been completed with an exceptional group of investors, which share our vision of improving the lives of cancer patients."

On July 22, 2020 Cullinan Oncology, LLC reported the launch of Cullinan Amber, a company focused on developing a next generation immuno-oncology platform to enhance the therapeutic window of immune-stimulatory cytokine combinations for the treatment of cancer (Press release, Cullinan Oncology, JUL 22, 2020, View Source [SID1234562254]). Cullinan Amber has acquired an exclusive license from the Massachusetts Institute of Technology for technology based on the seminal work of K. Dane Wittrup, the C. P. Dubbs Professor in Chemical Engineering and Biological Engineering, to develop novel multifunctional constructs that are retained in the tumor microenvironment via collagen binding, which enables prolonged local activity of immunostimulatory cytokine combinations. Cullinan Amber’s lead program is a single agent comprised of two potent antitumor cytokines, interleukin-12 (IL-12) and interleukin-2 (IL-2), along with a collagen-binding domain. IND-enabling studies are expected to commence in 2H20.

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"We are delighted to have the opportunity to work with Dane and his team," stated Patrick Baeuerle, Chief Scientific Officer, Biologics and co-founder of Cullinan Oncology. "The Wittrup lab has developed a pioneering approach that we believe has the potential to combine and finally enable pro-inflammatory cytokines to realize their full potential as effective, safe and well-controlled cancer therapeutics."

"Historically, numerous studies have shown that cytokine combinations, including IL-12 and IL-2, can synergistically enhance both innate and adaptive immunity, and mediate impressive antitumor activity across a range of preclinical tumor models," stated Jon Wigginton, Chief Medical Officer of Cullinan Oncology. "Clinically, however, many cytokines have been limited by systemic toxicity, and were developed without the benefit of key learnings regarding dosing, supportive care and patient selection that have emerged in the field of immuno-oncology."

To address this challenge, the Wittrup Lab, as described in a groundbreaking publication in the June 2019 issue of Science Translational Medicine (Momin et al., 26 June 2019), fused various cytokines to a collagen-binding protein and injected them directly into the tumor, which effectively retained the cytokines locally, minimized their systemic dissemination and toxicities, and prolonged their anti-tumor activity. Most importantly, non-injected tumors likewise shrank in response to therapy due to the induction of a systemic immune response.

On July 22, 2020 Novocure (NASDAQ: NVCR) reported that the first patient has been enrolled in its EF-33 phase 2 pilot trial of Tumor Treating Fields delivered utilizing high-intensity arrays in patients with recurrent glioblastoma (GBM) (Press release, NovoCure, JUL 22, 2020, View Source [SID1234562253]). Tumor Treating Fields is a cancer therapy that uses electric fields tuned to specific frequencies to disrupt cell division.

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Tumor Treating Fields survival benefit has shown a positive correlation with electric field intensity. The Optune system currently delivers Tumor Treating Fields therapy for the treatment of GBM using four transducer arrays with nine ceramic discs each. To increase field intensity, Novocure designed high-intensity arrays with 14 ceramic discs each for use in the EF-33 study. Increasing the surface area of the array is expected to enable delivery of higher field intensities while maintaining the treatment’s safety profile.

"Building upon a foundation of compelling preclinical and clinical evidence, we continue to expand our product development programs to support our mission to extend survival in some of the most aggressive forms of cancer," said William Doyle, Novocure’s Executive Chairman. "We believe we have a considerable opportunity to improve Tumor Treating Fields delivery systems through product innovation and are very pleased to bring the first high-intensity arrays to the clinic. We look forward to sharing data from these programs in future quarters."

EF-33 is an open-label, single-arm clinical trial to study if Optune delivered at 200 kHz to the brain using high-intensity arrays in the treatment of recurrent GBM significantly improves the clinical outcomes of patients compared to using standard transducer arrays. The study will enroll 25 patients with a minimum follow-up of six months. Patients will remain on Optune until disease progression. The primary endpoint of EF-33 is progression free survival. Secondary endpoints include overall survival, progression free survival rate at six months, overall survival rate at one year and two years, overall radiological response, and severity and frequency of adverse events. All comparisons will be made against historical control data from Novocure’s EF-11 study. Final data from the study is expected in 2022, at which point Novocure will determine the appropriate regulatory pathway for potential commercial use.

About Optune

Optune is a noninvasive, antimitotic cancer treatment for GBM. Optune delivers Tumor Treating Fields to the region of the tumor.

Tumor Treating Fields is a cancer therapy that uses electric fields tuned to specific frequencies to disrupt cell division. Tumor Treating Fields does not stimulate or heat tissue and targets dividing cancer cells of a specific size. Tumor Treating Fields causes minimal damage to healthy cells. Mild to moderate skin irritation is the most common side effect reported. Tumor Treating Fields is approved in certain countries for the treatment of adults with GBM and in the U.S. for MPM, two of the most difficult cancer types to treat. The therapy shows promise in multiple solid tumor types – including some of the most aggressive forms of cancer.

Approved Indications (U.S.)

Optune is intended as a treatment for adult patients (22 years of age or older) with histologically-confirmed glioblastoma multiforme (GBM).

Optune with temozolomide is indicated for the treatment of adult patients with newly diagnosed, supratentorial glioblastoma following maximal debulking surgery, and completion of radiation therapy together with concomitant standard of care chemotherapy.

For the treatment of recurrent GBM, Optune is indicated following histologically- or radiologically-confirmed recurrence in the supratentorial region of the brain after receiving chemotherapy. The device is intended to be used as a monotherapy, and is intended as an alternative to standard medical therapy for GBM after surgical and radiation options have been exhausted.

Important Safety Information

Contraindications

Do not use Optune in patients with GBM with an implanted medical device, a skull defect (such as, missing bone with no replacement), or bullet fragments. Use of Optune together with skull defects or bullet fragments has not been tested and may possibly lead to tissue damage or render Optune ineffective.

Use of Optune for GBM together with implanted electronic devices has not been tested and may lead to malfunctioning of the implanted device.

Do not use Optune for GBM in patients known to be sensitive to conductive hydrogels. Skin contact with the gel used with Optune may commonly cause increased redness and itching, and may rarely lead to severe allergic reactions such as shock and respiratory failure.

Warnings and Precautions

Optune can only be prescribed by a healthcare provider that has completed the required certification training provided by Novocure.

The most common (≥10%) adverse events involving Optune in combination with chemotherapy in patients with GBM were thrombocytopenia, nausea, constipation, vomiting, fatigue, convulsions, and depression.

The most common (≥10%) adverse events related to Optune treatment alone in patients with GBM were medical device site reaction and headache. Other less common adverse reactions were malaise, muscle twitching, and falls related to carrying the device.

If the patient has an underlying serious skin condition on the treated area, evaluate whether this may prevent or temporarily interfere with Optune treatment.

Do not prescribe Optune for patients that are pregnant, you think might be pregnant or are trying to get pregnant, as the safety and effectiveness of Optune in these populations have not been established.

On July 22, 2020 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, reported that performed a pooled analysis of the data from the Phase 1b/2 trial combining TG4001, a HPV16 targeted therapeutic vaccine, with avelumab (BAVENCIO), a human anti-PD-L1 antibody, in HPV16-positive recurrent and/or metastatic malignancies (Press release, Transgene, JUL 22, 2020, View Source [SID1234562252]). This analysis confirms that TG4001 can be safely combined with an immune checkpoint inhibitor and shows clinical activity of this combination regimen. The trial is being conducted in collaboration with Merck KGaA, Darmstadt, Germany, and Pfizer.

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The purpose of this exploratory Phase 1b/2 trial was to evaluate the safety and efficacy of the combination of TG4001 and an immune checkpoint inhibitor in a heterogeneous group of patients with aggressive, recurrent and/or metastatic HPV16-positive cancer. Clinical activity was observed in the overall study population (34 evaluable patients with oropharyngeal, anal, cervical, or other HPV16-positive cancers). In addition, Transgene has identified a selection criterion corresponding to patients showing particularly promising clinical activity in this trial. 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 [*].

Consistent with data presented at ESMO (Free ESMO Whitepaper) 2019 [1], durable responses have been observed 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 has stopped the trial in its current design. The Company intends to continue the clinical development of TG4001 in a larger, controlled confirmatory study.

All patients enrolled in the trial had an aggressive, recurrent and/or metastatic HPV16+ cancer that had progressed after one to three lines of chemotherapy. As previously reported [1], no new safety signals were observed.

Commenting on this novel immunotherapy regimen, Prof. Christophe Le Tourneau, MD, Head of the Department of Drug Development and Innovation (D3i) at the Curie Institute, and Principal Investigator of the trial, added: "The first results from this exploratory Phase 1b/2 trial are clearly encouraging. I believe that the response rate and the clinical outcomes of the combination compare favorably with existing standards of care and the historical data reported with immune checkpoint inhibitors alone."

"Patients with HPV16-induced cancers still do not have access to approved treatments designed to address the viral origin of their disease. We believe these data establish the clinical proof-of-concept of combining TG4001 with an immune checkpoint inhibitor. Based on these promising findings, Transgene intends to continue the clinical development of TG4001 in a larger, controlled confirmatory study and provide a better treatment option to this patient population," added Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene.

About the trial

This multi-center, open-label trial is assessing the safety and efficacy of this immunotherapy combination regimen (TG4001 + avelumab) in patients with HPV16 positive cancers who have disease progression on at least one line of systemic treatment for recurrent/metastatic disease (NCT03260023). Prof. Christophe Le Tourneau, M.D., PhD, Head of the Department of Drug Development and Innovation (D3i) at the Curie Institute, and a world expert in drug development and head and neck cancers, is the Principal Investigator of the study. The trial is being conducted in collaboration with Merck KGaA, Darmstadt, Germany, a leading science and technology company which in the US and Canada operates its biopharmaceutical business as EMD Serono, and Pfizer Inc (NYSE: PFE).

Patients received TG4001 at the dose of 5×107 pfu, SC, weekly for 6 weeks, every 2 weeks up to M6, and every 12 weeks thereafter, in combination with avelumab at 10 mg/kg, IV every two weeks, until disease progression.

The primary endpoint of the Phase 2 part is the overall response rate (ORR, using RECIST 1.1). Secondary endpoints include progression-free survival, overall survival, disease control rate and other immunological parameters.