On October 7, 2021 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported a clinical update of its wholly-owned, next-generation Bicycle Toxin Conjugates (BTCs), interim Phase I trial results for BT5528 and preliminary findings from the ongoing dose escalation portion of the BT8009 clinical trial (Press release, Bicycle Therapeutics, OCT 7, 2021, View Source [SID1234590937]).

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"We are pleased to provide a clinical update for two of our wholly-owned BTCs currently undergoing Phase 1 dose escalation trials in late line cancer patients," said Dominic Smethurst, MA, MBChB, MRCP, MFPM, Chief Medical Officer of Bicycle Therapeutics. "We are delighted to see preliminary anti-tumor activity in both trials and across two tumor types, as well as to report tolerability profiles that may demonstrate differentiation from antibody-based approaches."

"These data support our belief that the Bicycle platform offers a potentially differentiated approach to traditional toxin delivery. The data generated from these molecules provide a wealth of information and insights as we continue to expand the application of our technology and generate additional Bicycle- targeted therapeutics with the intention of making a meaningful difference to cancer patients," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "We look forward to providing additional clinical data on BT5528 and BT8009 next year, and initiating our Phase I/II study for BT7480 later this year."

BT5528, a BTC targeting EphA2, a target for which prior antibody-based approaches have been unsuccessful, has demonstrated preliminary anti-tumor activity. Bicycle has established an RP2D range and is pursuing enrollment in expansion cohorts

Preliminary signs of anti-tumor activity observed. A total of 24 patients were dosed both prior to, and after, the implementation of the EphA2 immunohistochemistry (IHC) assay, with a median of seven prior lines of therapy. Amongst these patients, preliminary anti-tumor activity was observed in urothelial and ovarian cancer patients.

A total of two BT5528 monotherapy urothelial patients were dosed. Both (100%) were observed to have tumor reductions constituting a partial response under Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The administered doses in these patients ranged from 6.5mg/m2 to 10 mg/m2 every other week.

A total of eight BT5528 monotherapy ovarian cancer patients were dosed. Of these eight, five were determined to be EphA2-positive based on the IHC assay. Anti-tumor activity was observed in four of the five (80%) patients, including one (20%) that constituted a partial response under RECIST version 1.1 criteria. The range of administered doses in these patients was 6.5- 8.5mg/m2 every other week.
Doses of BT5528 administered to date have been tolerated in the ongoing Phase I portion of the Phase I/II trial. In addition, and in contrast to the toxicities observed with MedImmune’s EphA2 antibody-drug conjugate (ADC) MEDI-547, Bicycle has observed no signs of coagulopathy to date.
Based on the Phase I results, Bicycle has established an RP2D range. BT5528 has been dosed up to 8.5mg/m2 every week and 10mg/m2 every other week. Some mild and transient neutropenia was observed at 8.5mg/m2 every week, although this did not constitute a DLT. At 10mg/m2 every other week, two DLTs were observed (Grade 3 fatigue and Grade 3 pneumonitis). The most common Grade 3 and above events were neutropenia, anemia and pneumonitis and there were two Grade 5 events: tumor lysis syndrome and renal failure caused by GI-related dehydration. Based on the totality of the findings, the RP2D is expected to be in the range of 6.5 mg/m2 to 8.5mg/m2 every other week, a dose that is believed to be within the therapeutic range based on both preclinical studies and preliminary clinical anti-tumor activity.
Bicycle to advance BT5528 in expansion cohorts. Based on the findings from the Phase I trial, Bicycle plans to initiate expansion cohorts in urothelial and ovarian cancers as well as a basket that includes head and neck, non-small cell lung, gastroesophageal and triple negative breast cancers in 2022. The trial will enroll up to 56 patients in the initial expansion cohorts, with the ability to further expand enrollment based on the results of the initial expansion cohorts.
BT8009, a Nectin-4 targeting BTC with a potentially differentiated profile as compared to a Nectin-4 targeting ADC has shown preliminary anti-tumor activity in the ongoing Phase I portion of its Phase I/II trial.

Preliminary signs of anti-tumor activity in urothelial patients observed. As of September 30, a total of 11 response evaluable urothelial cancer patients have been dosed in monotherapy cohorts of 2.5mg/m2 and 5.0mg/m2 weekly in the ongoing trial. Of these, four patients were in the 2.5mg/m2 dose cohort and seven in the 5.0mg/m2 dose cohort. Prior to enrollment, all patients had previously received at least two prior lines of therapy, with a median of two and a range of two-to-six prior therapies. A total of four patients (36%) were observed to have tumor reductions that constituted partial responses under RECIST 1.1, with a range in tumor reductions from 37% to 89% among these patients.

Four response evaluable patients were dosed at 2.5mg/m2 weekly. Among these four patients, three patients were observed to have at least stable disease, with a disease control rate of 75% and one patient (25%) was observed to have a tumor reduction of 37%, meeting the criteria of a partial response under RECIST 1.1.

Seven response evaluable patients were dosed at 5.0mg/m2 weekly. Among these seven patients, five were observed to have at least stable disease, with a disease control rate of 71% and three patients (43%) were observed to have tumor reductions meeting the criteria of a partial response under RECIST 1.1. The magnitude of tumor reductions ranged from 44% to 89%.
Dose escalation remains ongoing. At both 2.5mg/m2 weekly and 5.0mg/m2 weekly, BT8009 has been tolerated, with no DLTs observed to-date. At 5.0mg/m2 weekly, BT8009 is estimated to administer over 35% more MMAE per four-week dosing cycle compared to the antibody-based drug conjugate, enfortumab vedotin. The escalation remains ongoing, and patients are currently being enrolled in 7.5mg/m2 weekly and every other week cohorts.
BT8009 enrollment ongoing. A total of 14 clinical sites are active globally, including nine outside of the United States. Bicycle expects to have up to 21 sites active this year.
Conference Call Details

Bicycle Therapeutics will host a conference call and webcast on Thursday, October 7 at 3:00 p.m. ET to review the BT5528 trial data being presented at the AACR (Free AACR Whitepaper)-NCI-EORTC meeting and provide an update on preliminary findings from the BT8009 trial. To access the call, please dial (800) 377-9118 (domestic) or (409) 937-8920 (international) and provide the Conference ID 2287246. A live webcast of the presentation will be available on the Investors & Media section of the Bicycle website, bicycletherapeutics.com.

On October 7, 2021 NKGen Biotech, a biotechnology company harnessing the power of the body’s immune system through the development of Natural Killer (NK) cell therapies, reported that Stephen Chen, NKGen Biotech’s Chief Technical Officer, will present at the Virtual Solebury Trout Fall Private Company Showcase co-hosted with BMO, to be held October 14, 2021 (Press release, NKMax America, OCT 7, 2021, View Source [SID1234590936]).

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Details on the conference can be found below.

Virtual Solebury Trout Fall Private Company Showcase Co-hosted with BMO
Format: Company presentation
Date: Thursday, October 14, 2021
Presentation Time: 11:00 a.m. EDT [8:00 a.m. PDT]
Webcast: Click here to register

On October 7, 2021 IMV Inc. (NASDAQ: IMV; TSX: IMV), a clinical-stage biopharmaceutical company pioneering a novel class of immunotherapies against difficult-to-treat cancers, reported that the immunotherapeutic capabilities of its DPX delivery platform will be featured in two e-poster presentations at the AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) October 7-10, 2021 (Press release, IMV, OCT 7, 2021, View Source [SID1234590935]).

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"Collectively, these data demonstrate the versatility and potential of the DPX delivery platform to educate robust, targeted T cell responses to distinct cargo," said Jeremy Graff, Ph.D., Chief Scientific Officer at IMV. "More specifically, the first presentation provides compelling evidence that the DPX technology triggers a more consistent and persistent immune response than conventional emulsions. The second presentation provides the scientific basis for the clinical pursuit of DPX-SurMAGE, a new IMV asset designed to simultaneously elicit immune responses to the survivin and MAGE-A9 proteins, both of which have been implicated in bladder cancer progression."

Yves Fradet, M.D., Professor, Department of Surgery at the Faculty of Medicine, Université Laval in Quebec City commented, "The results obtained with IMV’s dual-targeted DPX-based immunotherapy, DPX-SurMAGE, in preclinical studies are very promising. I believe that patients with bladder cancer will benefit from this treatment while maintaining their quality of life."

Pre-clinical and clinical data presented at the conference show that:

The DPX technology represents a versatile delivery platform that generates robust T cell-based immune responses,
When packaged within the DPX platform, antigenic peptides are delivered and presented to the immune system in a manner that elicits specific T cell-based immune responses that are not achievable with conventional water-based emulsion delivery,
IMV’s lead compound, maveropepimut-S (MVP-S, previously known as DPX-Survivac) is well-tolerated in multiple clinical trials and effectively elicits a specific, robust, and persistent, survivin-specific T cell response evident most prominently in subjects showing greatest clinical benefit,
The DPX delivery platform can be leveraged to incite a T cell response to numerous tumor antigens simultaneously,
IMV’s dual-targeted immunotherapy, DPX-SurMAGE, is well tolerated and generates robust and targeted T cell responses against both survivin and MAGE-A9 peptides in preclinical models.
Collectively, these data provide evidence that the DPX delivery platform is a unique and versatile, immune-educating technology that can be applied in a variety of therapeutic areas where generation of a target-specific immune response is expected to mitigate disease.

Poster Presentation Details

Survivin peptides formulated in the DPX delivery platform rather than standard emulsions, elicit a robust, sustained T cell response to survivin in advanced and recurrent ovarian cancer patients.

Presenter: Yogesh Bramhecha, Ph.D.,
Director, Translational Research, IMV Inc.
Poster Number: LBA026
DPX-SurMAGE, a novel dual-targeted immunotherapy for bladder cancer, induces target-specific T cells with a favorable safety profile in preclinical studies

Presenter: Yves Fradet, M.D.
Professor, Department of Surgery
Faculty of Medicine, Université Laval, Quebec City
Poster Number: LBA030
Full abstracts and e-posters are available on demand on the conference platform. Both e-posters are available under the Scientific Publications & Posters section on IMV’s website.

On October 7, 2021 Aileron Therapeutics (Nasdaq: ALRN), a chemoprotection oncology company focused on fundamentally transforming the experience of chemotherapy for cancer patients, reported that new preclinical data at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) 2021 on ALRN-6924, currently in development as a novel, selective chemoprotective agent (Press release, Aileron Therapeutics, OCT 7, 2021, View Source [SID1234590934]). The new data demonstrated ALRN-6924’s activity as a radioprotective agent in preclinical mouse models of acute radiation-induced toxicity, leveraging the same mechanism of action – p53 activation and subsequent p21 upregulation as well as p21-induced cell cycle arrest – that has clinically shown protection against chemotherapy-induced toxicities.

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"Like chemotherapy, ionizing radiation is associated with serious, often dangerous side effects, as both chemotherapy and radiation destroy normal, healthy cells," said Manuel Aivado, M.D., Ph.D. "While preliminary, these new preclinical data suggest that ALRN-6924’s mechanism of action, which has demonstrated protection against chemotherapy-induced toxicities of the bone marrow, may also protect against radiation-induced toxicities. Furthermore, these preclinical studies provide our first evidence of ALRN-6924-mediated activation of p21 in epithelial mucosa cells in the GI tract, protecting irradiated mice from body weight loss, and the potential of ALRN-6924 to protect multiple tissues beyond the bone marrow from both chemotherapy and radiation-induced toxicities."

Dr. Aivado continued, "Developing ALRN-6924 as a selective chemoprotective agent in p53-mutated cancers continues to be our chief priority. Nonetheless, these encouraging preclinical data signal a potential future secondary application of ALRN-6924 complementing our ongoing chemoprotection program, and we look forward to conducting more research to further explore that possibility."

Aileron is currently developing ALRN-6924, a first-in-class MDM2/MDMX dual inhibitor, to selectively protect healthy cells in patients with cancers that harbor p53 mutations to reduce or eliminate chemotherapy-induced side effects while preserving chemotherapy’s attack on cancer cells. ALRN-6924 is designed to activate p53 in normal cells, which in turn upregulates p21, which pauses cell cycle in normal, healthy, proliferating cells but not in p53-mutated cancer cells.

In the AACR (Free AACR Whitepaper)-NCI-EORTC poster titled, "The Investigational Chemoprotection Drug ALRN-6924, a Dual Inhibitor of MDMX and MDM2, Shows Potential for Radioprotection" (Poster #P211), Aileron presented the results of preclinical studies designed to evaluate whether p53 activation with ALRN-6924 may protect healthy, proliferating cells in normal tissues from radiation-induced cellular toxicity.

In a non-lethal radiation exposure model, mice were exposed to a single dose of abdominally targeted radiation at 15 Gy following one or more doses/schedules of ALRN-6924 or placebo and then monitored for body weight. Aileron evaluated serum levels of macrophage inhibitory cytokine-1 (MIC-1), a biomarker of p53 activation, as well as biomarkers of p53-mediated cell cycle arrest (p21), and of apoptosis (cleaved poly-ADP-ribose polymerases, or cPARP) in mouse bone marrow and GI tract tissue. Repeated doses of ALRN-6924 administered every eight hours yielded sustained MIC-1 elevation, which correlated with increased p21 positivity in the bone marrow and intestine, while treatment-dependent changes in cPARP expression were minimal. Additionally, mice treated with ALRN-6924 had less radiation-induced body-weight loss than untreated mice. Mice receiving one or more doses of ALRN-6924 eight hours prior to irradiation had an average of 4% body weight loss, while placebo-treated mice had 10% to 15% body weight loss five days after irradiation. The poster will be archived on the Scientific Publications page of Aileron’s website at: View Source

Aileron is currently conducting a Phase 1b randomized, double-blind, placebo-controlled study of ARLN-6924 as a chemoprotective agent in the United States and Europe. The study is enrolling patients with advanced p53-mutated non-small cell lung cancer undergoing treatment with first-line carboplatin plus pemetrexed with or without immunotherapy. The company is pursuing a clinical development strategy designed to advance its vision to bring selective chemoprotection to all patients with p53-mutated cancer regardless of type of cancer or chemotherapy.

On October 7, 2021 IMMUNOPRECISE ANTIBODIES LTD. (the "Company" or "IPA") (NASDAQ: IPA) (TSX VENTURE: IPA) and the Pierre Fabre pharmaceutical group reported that IPA’s subsidiary, Talem Therapeutics LLC ("Talem"), and Pierre Fabre have entered a multi-year, multi-target research collaboration with the goal to discover and develop therapeutics antibodies for up to nine targets (Press release, ImmunoPrecise Antibodies, OCT 7, 2021, View Source [SID1234590933]). This strategic collaboration is expected to help expand Talem’s portfolio of novel antibodies across oncology. It adds to the variety of diverse relationships that the IPA group of companies holds across the pharmaceutical and biotechnology sector.

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Under the research collaboration, scientists from both companies will work together and contribute their respective resources to discover and develop novel antibodies leveraging the IPA group’s antibody discovery technologies, such as B cell Select or Deep Display using wild-type and/or transgenic animals, available human libraries, as well as their signature "end-to-end" services. The antibodies developed in the research collaboration against the selected targets will be jointly owned by Talem and Pierre Fabre and, following the completion of each target specific research program, Pierre Fabre will have an option to obtain an exclusive worldwide license to Talem’s interest in those jointly discovered antibodies against that particular target, and Talem would be eligible to receive certain up-front and contingent downstream payments. In addition, if licensed, Pierre Fabre will be responsible for the preclinical and clinical development, as well as the commercialization of the jointly discovered antibodies.

"Less than two years ago we started Talem Therapeutics to provide a unique partnering opportunity for companies to jointly seek the development of promising novel candidates," stated Dr. Stefan Lang, Chief Business Officer of ImmunoPrecise. "We are very excited to join forces with Pierre Fabre, combining our advanced antibody technologies with their world-class expertise in immuno-oncology is a powerful strategic combination enabling the teams to jointly address life threatening human diseases."
"Drug discovery in immuno-oncology is a priority for Pierre Fabre. We are therefore very pleased to enter this multi-target research collaboration. Talem will provide us with its expertise and a variety of technology platforms to enable the discovery of therapeutic antibodies, towards a set of structurally diverse targets." added Francesco Hofmann, Head of R&D at Pierre Fabre Medical Care.