On September 29, 2022 Kintor Pharmaceutical Limited ("Kintor Pharma", HKEX: 9939), a clinical-stage biotechnology company developing innovative small molecules and biological therapeutics, reported that the results from a phase Ib study of pruxelutamide (used to be called proxalutamide, GT0918) for the treatment of patients with androgen receptor positive (AR+) metastatic breast cancer (AR+ mBC) in China have been published in the international journal, European Journal of Cancer (2021 Impact Factor: 10.002, EJC) on September 28, 2022, further demonstrating the efficacy and safety of pruxelutamide in patients with AR+ mBC (Press release, Suzhou Kintor Pharmaceuticals, SEP 29, 2022, View Source [SID1234621572]).

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Highlights

Pruxelutamide showed promising activity in heavily pretreated AR+ mBC patients.
Pruxelutamide showed an acceptable safety profile in heavily pretreated AR+ mBC.
Recommended phase II dose of pruxelutamide was defined as 200mg orally once daily.
AR expression, cell-free DNA yield, CNV might be associated with response.
Patients with PIK3CA pathogenic mutation showed longer progression-free survival.
Metastatic breast cancer (mBC) remains a largely incurable disease in most patients, resulting in approximately 0.5 million deaths every year worldwide. At present, the primary goals of mBC therapy are to prolong patient survival and maintain their quality of life. Any novel therapy likely to provide a survival advantage in patients is valuable.

Pruxelutamide is an oral, newly-generation AR antagonist, developed by Kintor Pharma. Results from this study of pruxelutamide were published in a paper titled "Proxalutamide in patients with AR-positive metastatic breast cancer: Results from an open-label multicentre phase Ib study and biomarker analysis". This phase Ib study was designed to evaluate the preliminary efficacy and safety of pruxelutamide monotherapy in patients with pretreated AR+ mBC and to determine the RP2D of pruxelutamide. The corresponding author of the paper, Professor Huiping Li of Peking University Cancer Hospital & Institute, was the principal investigator of the phase I clinical trial in China.

In this open-label, dose-expansion, multicentre phase Ib trial, patients with AR+ mBC (immunohistochemistry [IHC] AR≥1%) received pruxelutamide orally once daily. Two pruxelutamide dose cohorts (cohort A: 200mg; cohort B: 300mg) were sequentially investigated. Primary endpoints were disease control rate (DCR) at 8 and 16 weeks and recommended phase II dose (RP2D).

Finally, 45 eligible patients were enrolled and treated. 30 eligible patients were enrolled in cohort A (200mg orally once daily) from April 19, 2018, to March 7, 2019. 15 patients were enrolled into cohort B (300mg orally once daily) from March 11, 2019, to April 16, 2019.

Among 39 evaluable patients, DCR at 8 and 16 weeks was 25.6% (95% confidence interval [CI], 11.9–39.4%), with 26.9% in cohort A and 23.1% in cohort B. The 6-month progression-free survival (PFS) rate was 19.6% (95% CI, 10.2–37.5%). In the triple-negative subgroup, DCR at 8 weeks was 38.5%, with median PFS of 9.1 months (95% CI, 7.8–NA) in those who achieved response at 8 weeks (n = 5).

All 45 patients were evaluable for safety. Overall, pruxelutamide demonstrated a good safety profile. The most common grade 3 or 4 AEs were AST increase (8.9%) and γ-glutamyltransferase increase (8.9%). No treatment-related deaths or dose reductions occurred in either cohort.

This study conducted another exploratory analysis to identify potential predictive biomarkers of treatment response. By biomarker analysis, patients with moderate AR expression of IHC (26%–75%), PIK3CA pathogenic mutations, or <60 ng/ml cell-free DNA yield showed longer PFS.

In conclusion, pruxelutamide demonstrated promising anti-tumour activity with an acceptable safety profile in patients with heavily pretreated AR+ mBC, particularly in the TNBC subgroup. And, this study determined the RP2D to be 200mg orally once daily. Furthermore, we identified that AR expression, CNVs, and cfDNA yield may be associated with the response to pruxelutamide, highlighting the importance of conducting genomic profiling in patients with AR+ mBC to identify those likely to benefit from pruxelutamide treatment. The data supports further clinical development of pruxelutamide on treating breast cancer patients.

On September 29, 2022 Kling Biotherapeutics, BV, (Kling Bio) a clinical stage biotechnology company focused on developing novel antibody-based therapeutics for cancer and infectious diseases generated through its proprietary discovery platform, reported the dosing of the first patient with KBA1412 in its Phase 1b trial (KBA1412-101, NCT05501821), an open-label, multi-center study evaluating the safety, tolerability, PK/PD, and potential efficacy of KBA1412 in adult patients with advanced solid tumors not responding to standard of care (Press release, Kling Biotherapeutics, SEP 29, 2022, View Source [SID1234621571]).

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KBA1412 is a first in class fully human anti-CD9 antibody based on an antibody produced by circulating B cells in the blood of a cancer survivor. "KBA1412 has remarkable properties identified in preclinical studies including efficacy as monotherapy mediated by two anti-cancer mechanisms (cell-mediated cytotoxicity and enhanced immune cell infiltration into tumors), synergy with PD-1 blockade, and a very favorable preclinical safety profile not seen previously with anti-CD9 antibodies" said Timothy M. Wright, MD, Kling Bio co-founder and interim CEO.

The Phase 1b study will involve dose escalation followed by several expansion cohorts in patients with selected solid tumor types. The expansion cohorts will study KBA1412 alone and in combination with a PD-1 checkpoint inhibitor to further define the dose for future Phase 2 studies and to evaluate secondary endpoints for preliminary assessment of clinical efficacy. "This study marks an important milestone for Kling Bio and demonstrates the potential to leverage the ‘human-to-human’ approach from discovery to clinical development for advancing novel cancer treatments," said Sohail Ahmed, MD, MBA, Chief Medical Officer at Kling Bio.

On September 29, 2022 Oxilio, a pioneering drug development company repurposing existing drugs to address unmet needs in cancer treatment, and Quotient Sciences, a drug development and manufacturing accelerator, reported an update on the development of Oxilio’s OXL001 product (Press release, Oxilio, SEP 29, 2022, View Source [SID1234621570]).

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Oxilio is pleased to announce that it has received approval from the UK Medicines and Healthcare products Regulatory Agency (MHRA) and Research Ethics Committee (REC) for its first Clinical Trial Application (CTA) with OXL001.

Following initial formulation development by Oxilio in collaboration with its partner company, TRx Biosciences, Quotient Sciences’ integrated Translational Pharmaceutics platform has been used to carry out the technical transfer and scale-up activities associated with this program and will continue to be used to support clinical trial material manufacturing and the investigation of the pharmacokinetics and safety of OXL001 in healthy volunteers.

Mark Egerton, PhD, CEO of Quotient Sciences, said: "We are delighted to be able to continue to assist Oxilio with their OXL001 program. By leveraging our unique, integrated Translational Pharmaceutics platform, Oxilio will have the flexibility to adjust doses based on emerging clinical data within their study, enabling us to improve their likelihood of success, reduce their development time, and ultimately get new medicines to patients faster."

Dr Simon Yaxley, Director of Oxilio, added: "Utilizing Quotient Sciences Translational Pharmaceutics platform has enabled us to successfully achieve this important milestone of receiving regulatory approval to undertake our first Phase 1 clinical trial with OXL001. We look forward to commencing this study within the next few weeks."

On September 29, 2022 Haleon plc ("Haleon") (LSE: HLN, NYSE: HLN) reported the commencement of offers to exchange seven series of outstanding unregistered notes issued by GSK Consumer Healthcare Capital US LLC (the "US Issuer") and GSK Consumer Healthcare Capital UK plc (the "UK Issuer", and together with the US Issuer, the "Issuers") (as set out below), as previously disclosed in Haleon’s public filings and pursuant to a registration rights agreement entered into at the time of the original issuance of the notes (Press release, Haleon Group, SEP 29, 2022, View Source [SID1234621569]).

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Upon the terms and subject to the conditions set forth in the prospectus and the accompanying letter of transmittal, Haleon is offering to exchange in seven concurrent, but separate, offers (the "Exchange Offers") any and all of the seven series of notes identified under "Title of Series of Original Notes" in the table below (collectively, the "Original Notes"), for a like principal amount of notes of the same series that have been registered under the Securities Act of 1933, as amended (the "Securities Act"), as described under "Title of Series of Exchange Notes" in the table below (collectively, the "Exchange Notes"). The terms of each series of Exchange Notes are substantially identical to the terms of the corresponding Original Notes of such series, except that the transfer restrictions, the special mandatory redemption provisions and registration rights applicable to the Original Notes do not apply to the Exchange Notes. The sole purpose of the Exchange Offers is to offer the holders of the Original Notes the opportunity to receive Exchange Notes that have been registered under the Securities Act and are expected to be listed on the New York Stock Exchange.

The Exchange Offers will expire at 5:00 p.m. (Eastern time) on October 28, 2022, unless extended or earlier terminated by Haleon (such date and time, as the same may be extended or earlier terminated with respect to any or all series of Exchange Notes (as defined below), the "Expiration Date"). In order to be exchanged, an Original Note must be validly tendered and not validly withdrawn at or prior to the applicable Expiration Date, and accepted by the relevant Issuer and Haleon. The "Settlement Date" with respect to the Exchange Offers will be promptly following the Expiration Date and is expected to be November 2, 2022.

A Registration Statement on Form F-4 (the "Registration Statement") relating to the issuance of the Exchange Notes was filed with the Securities and Exchange Commission ("SEC") today but has not yet been declared effective. The Exchange Offers are being made pursuant to the terms and conditions set forth in the preliminary prospectus, dated as of September 29, 2022 (the "Prospectus"), which forms a part of the Registration Statement.

Global Bondholder Services Corporation will act as Exchange Agent for the Exchange Offers. Questions or requests for assistance related to the Exchange Offers or for additional copies of the Prospectus may be directed to Global Bondholder Services Corporation at (855) 654-2014. You may also contact your broker, dealer, commercial bank, trust company or other nominee for assistance concerning the Exchange Offers.

If Haleon terminates any Exchange Offer with respect to one or more series of Original Notes, it will give prompt notice to the Exchange Agent, and all Original Notes tendered pursuant to such terminated Exchange Offer will be returned promptly to the tendering holders thereof. With effect from such termination, any Original Notes blocked in DTC will be released.

Notes issued by the US Issuer

Description of the Original Notes

Description of the Exchange Notes

CUSIP Number

Title of Series of Original Notes

CUSIP
Number

Title of Series of Exchange Notes

36264F AA9 /
U04020 AA8

3.024% Callable Fixed Rate Senior Notes due 2024

36264F AH4

3.024% Callable Fixed Rate Senior Notes due 2024

36264G AB5 /
U0396G AB9

Callable Floating Rate Senior Notes due 2024

36264F AJ0

Callable Floating Rate Senior Notes due 2024

36264F AB7/
U04020 AB6

3.375% Fixed Rate Senior Notes due 2027

36264F AK7

3.375% Fixed Rate Senior Notes due 2027

36264F AC5 /
U04020 AC4

3.375% Fixed Rate Senior Notes due 2029

36264F AL5

3.375% Fixed Rate Senior Notes due 2029

36264F AD3 /
U04020 AD2

3.625% Fixed Rate Senior Notes due 2032

36264F AM3

3.625% Fixed Rate Senior Notes due 2032

36264F AE1 /
U04020 AE0

4.000% Fixed Rate Senior Notes due 2052

36264F AN1

4.000% Fixed Rate Senior Notes due 2052

Notes issued by the UK Issuer

Description of the Original Notes

Description of the Exchange Notes

CUSIP Number

Title of Series of Original Notes

CUSIP
Number

Title of Series of Exchange Notes

36264N AA2 /
G4164D AA6

3.125% Fixed Rate Senior Notes due 2025

36264N AB0

3.125% Fixed Rate Senior Notes due 2025

Holders are advised to check with any bank, securities broker or other intermediary through which they hold Original Notes as to when such intermediary needs to receive instructions from a holder in order for that holder to be able to participate in, or (in the circumstances in which revocation is permitted) revoke their instruction to participate in, the Exchange Offers before the deadlines specified herein and in the documents pertaining to the Exchange Offers. The deadlines set by each clearing system for the submission and withdrawal of exchange instructions will also be earlier than the relevant deadlines specified herein and in the documents pertaining to the Exchange Offers.

The New Notes are not intended to be offered, sold or otherwise made available to and should not be offered, sold or otherwise made available to any retail investor in the European Economic Area (the "EEA"). For these purposes, a "retail investor" means a person who is one (or more) of: (i) a retail client as defined in point (11) of Article 4(1) of Directive (EU) 2014/65 (as amended, "MiFID II") or (ii) a customer within the meaning of Directive (EU) 2016/97(as amended, the "Insurance Distribution Directive"), where that customer would not qualify as a professional client as defined in point (10) of Article 4(1) of MiFID II. Consequently, no key information document required by Regulation (EU) No 1286/2014 (as amended, the "PRIIPs Regulation") for offering or selling the New Notes or otherwise making them available to retail investors in the EEA has been prepared and therefore offering or selling of the New Notes or otherwise making them available to any retail investor in the EEA may be unlawful under the PRIIPs Regulation.

Any offer of the New Notes in any member state of the EEA will be made pursuant to an exemption under Regulation (EU) 2017/1129 (as amended, the "Prospectus Regulation") from the requirement to publish a prospectus for offers of securities. This press release is not a prospectus for the purposes of the Prospectus Regulation.

The New Notes are not intended to be offered, sold or otherwise made available to and should not be offered, sold or otherwise made available to any retail investor in the United Kingdom (the "UK"). For these purposes, a "retail investor" means a person who is one (or more) of the following: (i) a retail client, as defined in point (8) of Article 2 of Regulation (EU) No 2017/565 as it forms part of UK domestic law by virtue of the European Union (Withdrawal) Act 2018 (the "EUWA"); or (ii) a customer within the meaning of the provisions of the Financial Services and Markets Act 2000 (as amended, the "FSMA") and any rules or regulations made under the FSMA to implement the Insurance Distribution Directive, where that customer would not qualify as a professional client, as defined in point (8) of Article 2(1) of Regulation (EU) No 600/2014 as it forms part of UK domestic law by virtue of the EUWA. Consequently, no key information document required by Regulation (EU) No. 1286/2014 as it forms part of UK domestic law by virtue of the EUWA (as amended, the "UK PRIIPs Regulation") for offering or selling the New Notes or otherwise making them available to retail investors in the UK has been prepared and therefore offering or selling the New Notes or otherwise making them available to any retail investor in the UK may be unlawful under the UK PRIIPs Regulation.

Any offer of the New Notes in the UK will be made pursuant to an exemption under Regulation (EU) 2017/1129 as it forms part of domestic law by virtue of EUWA (the "UK Prospectus Regulation") from the requirement to publish a prospectus for offers of securities. This press release is not a prospectus for the purposes of the UK Prospectus Regulation.

In the United Kingdom, this press release is being distributed only to, and is directed only at (i) persons who have professional experience in matters relating to investments falling within Article 19(5) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005 (as amended, the "Order"), and/or (ii) high net worth companies (or persons to whom it may otherwise be lawfully communicated) falling within Article 49(2)(a) to (d) of the Order (all such persons together referred to as "relevant persons"). This press release must not be acted on or relied on in the United Kingdom by persons who are not relevant persons. In the United Kingdom, any investment or investment activity to which this press release relates is only available to, and will be engaged in with, relevant persons only.

On September 29, 2022 Delphinus Medical Technologies, Inc. reported the closing of a $30 million Series D financing to fuel worldwide commercialization of its SoftVue 3D Whole Breast Ultrasound Tomography System (SoftVue) (Press release, Delphinus Medical Technologies, SEP 29, 2022, View Source [SID1234621568]). The round drew participation from both new and existing investors, including Arboretum Ventures, Beringea, North Coast Technology Investors, Venture Investors, Hopen Life Science Ventures and Waycross Ventures. The fund’s closing comes on the heels of the announcement that the first SoftVue System was sold, and will go to Karmanos Cancer Institute, Detroit, where the technology was originally conceived.

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"Every day it becomes increasingly obvious that we have delivered a game changer technology to transform dense breast screening," said Mark J. Forchette, president and CEO of Delphinus Medical Technologies. "When potential customers hear that SoftVue finds more cancers, delivers an exceptional patient experience and efficient patient workflow the same day as the mammogram without costly staff additions, they recognize the value for their patients. Our series D will support the robust commercial strategies and efforts needed to help sites quickly adopt this solution for their patients."

Forty percent of women in the U.S. have dense breast tissue, and they have a four-to-six-time greater risk of developing breast cancer. Mammography alone misses about half the cancers in women with dense breasts, as dense tissue and cancer both appear white on mammogram images. SoftVue was developed to address this unmet clinical need and provides a new annual screening solution for this historically underserved population.

SoftVue is indicated for use as an adjunct to digital mammography in the screening of asymptomatic women with dense breast tissue. SoftVue enhances dense breast screening and identifies up to 20% more cancers with greater accuracy and potentially fewer biopsies than full field digital mammography (FFDM) alone. The SoftVue exam is completed with no compression or radiation, and its PMA indication for use allows SoftVue exams to be performed at the same appointment as screening mammograms, facilitating a streamlined workflow and rapid delivery of results.

"Our board of directors and investors are very excited to launch into commercial activities with SoftVue," said Paul McCreadie, Delphinus Medical Technology’s board chairman and Partner and Chief Operating Officer at Arboretum Ventures. "The successful completion of a rigorous clinical study that resulted in the PMA approval we received last year for dense breast screening will allow the Delphinus team to leverage the unique technology of SoftVue to change the paradigm for dense breast screening and help millions of women receive superior care. We invest to allow breakthrough innovations to serve patients, and Delphinus is perfectly poised to do exactly that."