On October 21, 2021 Longbow Immunotherapy, a newly formed biotech advancing solid tumor therapy, reported its formation and exclusive license of the ReACT platform from the Versiti Blood Research Institute (Press release, Longbow Immunotherapy, OCT 21, 2021, View Source [SID1234591755]).

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ReACT (Re-energized adoptive cell transfer), combines CAR-T cell therapy with microbial immunotherapies, such as bacteria and oncolytic viruses, to synergistically treat solid tumors. Invented by Dr. Weiguo Cui, senior investigator, Versiti Blood Research Institute, ReACT T cells possess tumor targeting receptors as well as an added receptor that extends T cell activity when in the presence of tumor specific microbial immunotherapies. Its advantages include modification of the tumor microenvironment, localized activity, broad targeting of tumor antigens, and prevention of T cell exhaustion.

Longbow’s initial target for ReACT is bladder cancer, where Dr. Cui has engineered immune cells to express a novel CAR recognizing BCG, the standard of care in post resection bladder cancer therapy. The ReACT-BCG construct has been evaluated in a mouse model of bladder cancer, where it showed significant improvements in survival, tumor volume and immune cell markers. Dr. Cui said, "Currently, 60% of bladder cancer patients will experience recurrence within two years of tumor resection. ReACT has the potential to radically improve the prognosis for these patients."

Longbow also plans to extend the application of ReACT beyond initial bladder cancer uses, as ReACT T cells can be engineered to recognize and synergize with any bacterial immunotherapy or oncolytic virus targeting solid tumors. Kurt Rote, Co-Founder, stated, "For years, the field has been wanting to combine immunotherapy bacteria and oncolytic virus with CAR-T cells. Longbow is doing so in a novel, synergistic fashion, and is dedicated to getting this promising treatment to patients."

On October 21, 2021 Ultimovacs ASA ("Ultimovacs") (OSE ULTI), a clinical-stage leader in immune stimulatory vaccines for cancer, reported its universal cancer vaccine, UV1, in combination with checkpoint inhibitors has received Fast Track designation from the U.S. FDA in the treatment of unresectable or metastatic melanoma – either as add-on therapy to pembrolizumab or as add-on therapy to ipilimumab (Press release, Ultimovacs, OCT 21, 2021, View Source [SID1234591774]). Ultimovacs is currently evaluating UV1 as add-on therapy to ipilimumab and nivolumab as first-line treatment for unresectable or metastatic melanoma in a Phase II study named INITIUM.

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Ultimovacs senior management will host a webcast on the Fast Track designation and the supporting clinical data at 13.00 CET on Thursday October 21.

The FDA Fast Track process is designed to facilitate the development and expedite the review of drugs that meet urgent needs in serious medical conditions. Fast Track designation enables early and frequent communication with the FDA to support the drug’s development, as well as entitlement to a Rolling Review of the Biologic License Application. Drugs with Fast Track designation may also be considered for Accelerated Approval and Priority Review provided certain criteria are met.

"We are delighted UV1 has received the Fast Track designation and look forward to working more closely with the FDA to bring UV1 to melanoma patients as soon as possible," said Carlos de Sousa, Chief Executive Officer of Ultimovacs. "The FDA’s decision recognizes the potential synergy of UV1 and checkpoint inhibitors and will greatly encourage physicians and patients involved in our Phase II clinical trial INITIUM. We remain committed to progressing UV1 in our four ongoing Phase II clinical studies and assessing development of UV1 with pembrolizumab in advanced melanoma."

The Fast Track designation is based on data from two separate Phase I trials of UV1 in combination with checkpoint inhibitors, either with pembrolizumab (anti-PD-1) or with ipilimumab (anti-CTLA-4). According to data disclosed recently, UV1 in combination with pembrolizumab as a first-line treatment in advanced melanoma was shown to be safe with promising early efficacy data; an objective response rate (ORR) of 57% was reached with 30% of patients achieving a complete response (CR), or complete disappearance of their tumors. At 24 months follow up, 80% of patients were alive. In a second cohort, similar levels of tumor destruction were seen with 90% of patients remained alive after one year. Peer-reviewed data published in May 2021 in Frontiers in Immunology demonstrated that UV1 with ipilimumab was safe and showed signals of prolonged efficacy in advanced melanoma, the combination achieving ORR of 33% and 5-year overall survival (OS) rate of 50%.

UV1 is currently being investigated in combination with checkpoint inhibitors in four Phase II trials: in unresectable or metastatic melanoma, ovarian cancer, head and neck squamous cell carcinoma and malignant pleural mesothelioma.

Ultimovacs’ webcast on the Fast Track designation and clinical data at 13.00 CET (7.00 am EST) on Thursday 21 October 2021 will be accessible here and from the company website.

On October 21, 2021 Selecta Biosciences, Inc. (NASDAQ: SELB), a biotechnology company leveraging its clinically validated ImmTOR platform to develop tolerogenic therapies that selectively mitigate unwanted immune responses, and Genovis (GENO), an enzyme technology company, reported a strategic licensing agreement to advance a next-generation IgG protease (Press release, Selecta Biosciences, OCT 21, 2021, View Source [SID1234591674]). This partnership leverages Genovis’ proprietary immunoglobulin G (IgG) protease, IdeXork (Xork), and Selecta’s ImmTOR platform to enable the dosing of transformative gene therapies in patients with pre-existing adeno-associated virus (AAV) immunity and treat certain IgG-mediated autoimmune diseases.

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Most IgG proteases are derived from human pathogens and have a high prevalence of pre-existing antibodies. Xork is derived from a Streptococcal bacterial strain that does not infect humans. The pre-clinical data generated to date highlights Xork’s differentiated profile – demonstrating very low cross-reactivity with naturally occurring antibodies in human sera while retaining efficient and specific cleavage of human IgG antibodies.

Currently, pre-existing IgG antibodies against AAV gene therapy vectors are a major exclusion criterion for AAV gene therapy eligibility, affecting upwards of 40% of the population. Additionally, de novo immunogenicity that follows treatment by AAV gene therapy results in the formation of high titers of neutralizing antibodies. These neutralizing antibodies preclude re-treatment of those patients who may need additional dosing to maintain therapeutic benefit. The combination of Xork and ImmTOR has the potential to both mitigate pre-existing antibodies to AAV, expanding access to gene therapy to a wider range of patients, and prevent de novo immunogenicity, keeping patients eligible for re-treatment.

Additionally, bacterial-derived IgG proteases are themselves immunogenic. Currently, IgG proteases can only be administered once due to the formation of high titer antibodies against the protease itself. The combination of Xork and ImmTOR is further differentiated by the potential of ImmTOR to mitigate the immunogenicity of Xork and enable re-dosing of Xork, an important benefit for the application of IgG proteases in autoimmune diseases mediated by pathogenic autoantibodies.

Fredrik Olsson, chief executive officer of Genovis, commented, "We are excited to partner with Selecta as we look to expand into the gene therapy field and address the challenge of pre-existing immunity to AAV vectors. While IgG proteases have shown promise, overcoming the immunogenicity of the enzyme remains a significant hurdle. We believe Selecta’s ImmTOR platform, which is designed to mitigate unwanted immune responses, in combination with Xork has the potential to be transformational in both gene therapies and autoimmune diseases."

"We see this strategic collaboration with Genovis as an important step in expanding our pipeline of novel therapeutics in combination with our ImmTOR platform," said Carsten Brunn, Ph.D., president and chief executive officer of Selecta. "Our preclinical findings in gene therapy indicate that ImmTOR has the potential to increase transgene expression and durability, enable re-dosing by inhibiting the formation of neutralizing antibodies and potentially lead to safer, more efficacious gene therapy treatment regimens. The partnership between Selecta and Genovis focuses on those patients who would otherwise be unable to be treated due to pre-existing immunity to AAV. The combination of ImmTOR with Xork has the potential to significantly expand access to life changing gene therapies for those patients in need."

Terms of agreement
Under the terms of the agreement, Selecta has provided Genovis with an upfront payment for an exclusive license to Xork for all therapeutic uses in humans while Genovis retains rights to research, preclinical, diagnostic, and other potential non-therapeutic applications of Xork. Additionally, Genovis is eligible to earn development and sales-based milestones, as well as tiered royalties on worldwide sales in the low double digits.

On October 21, 2021 PDS Biotechnology Corporation (Nasdaq: PDSB), a clinical-stage immunotherapy company developing novel cancer therapies based on the Company’s proprietary Versamune T-cell activating technology, reported the temporary suspension of recruitment in the National Cancer Institute (NCI)-led Phase 2 clinical trial (NCT04287868) evaluating PDS0101 (Versamune-HPV16) in combination with two investigational immune-modulating agents in advanced HPV cancers (Press release, PDS Biotechnology, OCT 21, 2021, View Source [SID1234591693]).

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The issue is not specific to the PDS0101 trial and is unrelated to any safety or efficacy concerns with the triple combination. The NCI anticipates that the issue should be resolved timely, at which time the PDS0101 trial recruitment will resume. The timing of clinical data resulting from this trial is not expected to be affected by the recruitment suspension.

"We know from the interim data that this combination has the potential to significantly improve clinical outcomes for patients with advanced, refractory HPV16-associated cancers who have limited treatment options. While the trial is experiencing a slight administrative delay, we are pleased to report that the PDS0101 trial recruitment has progressed well and it is anticipated that it will resume recruitment shortly. We believe based on the previously reported results, that this treatment could significantly improve survival benefit for these patients, and we look forward to resumption of the trial in the near term," said Dr. Lauren V. Wood, PDS Biotech’s Chief Medical Officer.

The trial is evaluating the novel combination in both checkpoint inhibitor naïve and refractory patients with advanced HPV-associated cancers that have progressed or returned after treatment. The vast majority of these cancers are caused by HPV16.

On October 21, 2021 RefleXion Medical, a therapeutic oncology company pioneering biology-guided radiotherapy* (BgRT) as a new modality for treating all stages of cancer, reported multiple clinical abstracts evaluating the potential use and utility of its novel technology were accepted for presentation during the American Society for Radiation Oncology (ASTRO) 2021 Annual Meeting, Oct. 24-27, in Chicago (Press release, RefleXion Medical, OCT 21, 2021, View Source [SID1234591717]). The company will showcase technology from the RefleXion X1 machine in its booth, #1309.

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"Particularly gratifying among our multiple abstracts are oral presentations demonstrating physical validation of biological guidance for delivering radiotherapy to an FDG-avid target and exploring whether novel prostate surface membrane antigen radiotracers hold promise for one day enabling BgRT in prostate cancer," said Shervin ‘Sean’ Shirvani, M.D., M.P.H., chief medical officer at RefleXion. "Also, our earliest clinical adopters are presenting work detailing commissioning of the very first commercial X1 machine, which has delivered hundreds of fractions of conventional radiotherapy, a critical step toward bringing BgRT to the clinic."

The following presentations taking place during ASTRO 2021 evaluate RefleXion’s X1 technology:

Sunday, Oct 24: Radiation and Cancer Physics

1:55 PM 1002 "Feasibility of using FDG in the Stereotactic Ablative Setting for Tracked Dose Delivery with BgRT: Results from a Prospective Study of Serial Inter-Fraction PET/CTs." (Oral Abstract, Room 178 a/b)
4:45 PM 2248 Poster Q&A 02 – Session 02 – "Dosimetric comparison of single-isocenter and multiple-isocenter techniques for two-lesion lung SBRT using the RefleXion high-speed ring-gantry system." (Room W375)
Monday, Oct 25, 11:20 AM: Radiation and Cancer Physics

40 "Physical validation of biology-guided radiotherapy for delivering a tracked dose distribution to a moving PET-avid target." (Oral Abstract, Room 184 a/b/c/d)
Tuesday, Oct 26:

1:30 PM 98 Radiation and Cancer Physics "Evaluation of PSMA-PET biology-guided radiotherapy sequential boost to the dominant intraprostatic lesion in low-volume advanced prostate cancer." (Oral Abstract, Room W185 a/b/c/d)
3:30 PM Poster Q&A 08 – Session 08 – Lung Cancer/Thoracic Malignancies and Palliative Care. (Outside Room 375)
2883 "Disease Burden on FDG-PET Predicts Outcomes for Advanced Non-Small Cell Cancer Patients Treated with First-Line Immunotherapy."
2884 "Characterization of the Entire Metastatic Spectrum for Non-Small Cell Lung Cancer in the Immunotherapy Era."
Wednesday, Oct. 27, 10:30 AM: Poster Q&A 09 – Session 09 – Physics Treatment Techniques and Patient Safety (Outside Room 375)

3067 "First Beam Commissioning Report of a Novel Medical Linear Accelerator Designed for Biologically Guided Radiotherapy."
3069 "Physical Confirmation of Biology-guided Radiotherapy Directed at Static Targets with Varying Shapes and Background Contrast Environments."
3074 "Comparison of a First-in-class LINAC-integrated PET System and a Diagnostic PET/CT Scanner."
3075 "Initial Evaluation of Biology-guided Radiotherapy (BgRT) Plans Generated Using PET Acquired on the First Installation of Reflexion X1 System."
3115 "The kVCT System Commissioning of a Novel Medical Linear Accelerator Designed for Biology-guided Radiotherapy."
3138 "Utilizing Biology-guided Radiotherapy for Coronary Artery Avoidance During Free-breathing External Beam Radiation Delivery."