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 ProfoundBio reported that preclinical data from its novel, proprietary ADC technology platform are being presented at the 2021 Molecular Targets and Cancer Therapeutics conference hosted by the American Association for Cancer Research (AACR) (Free AACR Whitepaper), the National Cancer Institute (NCI), and the European Organisation for Research and Treatment of Cancer (EORTC) (Press release, ProfoundBio, OCT 7, 2021, View Source [SID1234590959]). The presentation is entitled, "Novel Hydrophilic Drug Linkers Enable Exatecan-based Antibody-Drug Conjugates with Promising Physiochemical Properties and In Vivo Activity."

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"Our platform enables us to develop ADCs that could otherwise not even be considered for development. By optimizing physiochemical properties, our platform enables the use of hydrophobic payloads at a drug to antibody ratio (DAR) up to 8, and potentially higher, while maintaining similar pharmacokinetics to unconjugated mAb, robust anti-tumor activity, and an acceptable safety profile," said Baiteng Zhao, PhD, Chief Executive Officer at ProfoundBio. "This technology has the potential to usher in a new generation of ADCs that will meaningfully help patients who have cancer."

On October 7, 2021 Kyowa Kirin Co., Ltd. (TSE:4151, President and CEO: Masashi Miyamoto, "Kyowa Kirin") reported the discontinuation for developing KHK2375 (generic name: entinostat) (Press release, Kyowa Hakko Kirin, OCT 7, 2021, View Source [SID1234590979]).

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KHK2375 is a Class I selective histone deacetylase (HDAC) inhibitor, which was discovered by Syndax Pharmaceuticals Inc. Kyowa Kirin signed a license agreement with Syndax Pharmaceuticals Inc. for the exclusive rights to the development and commercialization of KHK2375 in Japan and Korea in 2014.

Under the license agreement, Kyowa Kirin developed KHK2375 for indications of breast cancer in its territory. However, concerning the situation carefully, Kyowa Kirin discontinued KHK2375 development project.

Yoshifumi Torii, Ph.D., Executive Officer, Vice President, Head of R&D Division of Kyowa Kirin commented, "We are disappointed in this decision, as it was expected to have novel possibilities in breast cancer treatment, especially in endocrine therapy. We would like to express our appreciation to all the patients and investigators who contributed to the clinical studies and our development and continue to push forward to deliver therapies that meet unmet medical needs in oncology."

The Kyowa Kirin Group companies strive to contribute to the health and well-being of people around the world by creating new value through the pursuit of advances in life sciences and technologies.

On October 7, 2021 Pyxis Oncology, Inc. (Nasdaq: PYXS), a preclinical oncology company focused on developing an arsenal of next-generation therapeutics to target difficult-to-treat cancers and improve quality of life for patients, reported the pricing of its upsized initial public offering of 10,500,000 shares of common stock at an initial public offering price of $16.00 per share (Press release, Pyxis Oncology, OCT 7, 2021, View Source [SID1234591034]). All of the shares are being offered by Pyxis. The gross proceeds from the offering, before deducting underwriting discounts and commissions and other offering expenses payable by Pyxis, are expected to be $168.0 million. The shares are expected to begin trading on the Nasdaq Global Select Market on October 8, 2021 under the ticker symbol "PYXS." The offering is expected to close on October 13, 2021, subject to the satisfaction of customary closing conditions. In addition, Pyxis has granted the underwriters a 30-day option to purchase up to an additional 1,575,000 shares of common stock at the initial public offering price, less underwriting discounts and commissions.

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BofA Securities, Jefferies, Credit Suisse and William Blair are acting as joint book-running managers for the offering. LifeSci Capital is also acting as an underwriter for the offering.

Registration statements relating to the offering have been filed with the Securities and Exchange Commission and became effective on October 7, 2021. The offering will be made only by means of a prospectus. When available, copies of the final prospectus may be obtained from BofA Securities, NC1-004-03-43, 200 North College Street, 3rd Floor, Charlotte, North Carolina 28255-0001, Attention: Prospectus Department, or by email at [email protected]; from Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, or by email at [email protected] or by telephone at 877-821-7388; from Credit Suisse Securities (USA) LLC, Attn: Prospectus Department, 6933 Louis 31 Stephens Drive, Morrisville, North Carolina 27560, Telephone:1-800-221-1037, or by email at [email protected]; or from William Blair, Attention: Prospectus Department, 150 North Riverside Plaza, Chicago, IL 60606, or by telephone at(800) 621-0687 or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any offer or sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

On October 7, 2021 AbClon (174900, CEO Jong-seo Lee) a bio venture company and Ebixgen(CEO Yoo Ji-chang) reported a business agreement(MOU) on joint research and development of antibody new drugs with increased tissue permeability (Press release, AbClon, OCT 7, 2021, View Source;wr_id=148&page=2 [SID1234638670]). It was announced on 07 that the agreement was concluded. The two companies signed an MTA (material transfer agreement >, last 8month)With this MOU, we will continue to promote joint research and development of new antibody drugs.

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An official of AbClon said, "According to this agreement, Antibodies discovered using AbClone’s antibody and epitope discovery technologyNESTplatform are transferred to Ebixgen’s drug delivery platform. We plan to conduct joint research to develop new antibody drugs that increase the cell delivery ability of drugs by applying them to ACP"< /span>. "by developing innovative new antibody drugs with improved pharmacological efficacy and safety. He emphasized, "We expect to be able to expand to areas that existing antibody treatments cannot solve" said

AbClon is a specific epitope of an antigen(binding site) NEST (Novel Epitope), a technology to discover antibodies that bind to Screening Technology) has a platform. Via the NESTplatform Discovered AC101(stomach cancer, breast cancer antibody treatment< a i=13>) is affiliated with Shanghai Henlius Biotech(Shangahi Henlius Biotech) in China. Technology transfer(L/O)year and clinical trial2ahead. . In addition, its own antibody that binds to a new epitope of the disease protein CD19 Developed, applied it CAR-T cell therapy IND< /span>. month6 It was submitted last Phase1 Domestic clinical trial of AT101

Ebixgen possesses ACP (Advanced Cell Penetrating Peptide technology)technology, which is a new drug development platform technology and next-generation cell and tissue penetration delivery technology. Doing. This is a technology that improves the penetration and delivery ability of drugs that act on cells and tissues. In particular, the blood-brain barrier of drugs(BBB) ​​increasing the permeability of drugs, which is the biggest challenge in the development of existing treatments for brain diseases a>BBB It is characterized by being able to solve the transmission problem. Also, several poorly soluble It can dramatically increase the low solubility, which is a limitation of the drug, thereby increasing the usefulness of poorly soluble drugs with limited application. It is a technology that can expand and improve indications. The company currently treats AIDS, age-related macular degeneration, dry eye disease, < /span>. We have a variety of pipelines, including treatments for atopic dermatitis.

Meanwhile, cell and tissue penetration of drugs, etc. Involved’Drug Delivery System(DDS, Drug Delivery System)’ Is As the final stage of new drug development, controlling the speed of drug application and minimizing side effects are the key to technological prowess . Depending on the size or charge of the new drug candidate, the drug There are many cases where it cannot pass through the inside of the cell, and various DDS Technology is being researched.