On October 6, 2022 Domain Therapeutics ("Domain" or "the Company"), a drug discovery and development company focused on G Protein-Coupled Receptors (GPCRs) in immuno-oncology, reported that it will present data on its proprietary GPCR programs at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (STIC) Annual Meeting, taking place on 8-12 November 2022 in Boston, US (Press release, Domain Therapeutics, OCT 6, 2022, View Source [SID1234622444]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Domain will present two posters on its oral small molecule EP4R antagonist, DT-9081. The first poster will highlight preclinical data illustrating the synergy of DT-9081 in combination with immune checkpoint inhibitors in different cancer models. The second poster will focus on the clinical trial design for the upcoming Phase I clinical study, which is expected to start before the end of the year.

Domain will also present a poster on its CCR8 depleting-antibody program illustrating key differentiating properties of its patent-protected proprietary series of antibodies targeting CCR8. It’s known that this GPCR is specifically expressed on tumor-infiltrating regulatory T cells, a highly immuno-suppressive cell population driving tumor progression. This target is currently attracting significant interest for the development of novel game-changing immunotherapies.

Dr. Stephan Schann, VP Research at Domain Therapeutics, commented: "The data to be presented will highlight the potential of our proprietary GPCR programs as attractive immuno-oncology drug candidates. We look forward to presenting these exciting new findings which will demonstrate the potential advantages of our drug candidates, whilst positioning Domain Therapeutics as key player in the field of immunotherapies."

On October 6, 2022, Propanc Biopharma, Inc. (the "Company") reported that it entered into a securities purchase agreement (the "Purchase Agreement") with Red Road Holdings Corporation, a Virginia corporation ("Red Road"), pursuant to which Red Road purchased a convertible promissory note (the "Note") from the Company in the aggregate principal amount of $53,750, such principal and the interest thereon convertible into shares of the Company’s common stock at the option of Red Road (Filing, 8-K, Propanc, OCT 6, 2022, View Source [SID1234621942]). The transaction contemplated by the Purchase Agreement closed on October 12, 2022. The Company intends to use the net proceeds ($50,000) from the Note for general working capital purposes.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The maturity date of the Note is October 6, 2023 (the "Maturity Date"). The Note shall bear interest at a rate of 8% per annum, which interest may be paid by the Company to Red Road in shares of common stock, but shall not be payable until the Note becomes payable, whether at the Maturity Date or upon acceleration or by prepayment, as described below. Red Road has the option to convert all or any amount of the principal face amount of the Note, beginning on the date which is one hundred eighty (180) days following the date of this Note and ending on the later of: (i) the Maturity Date and (ii) the date of payment of the Default Amount (as defined below), each in respect of the remaining outstanding amount of this Note, to convert all or any part of the outstanding and unpaid amount of this Note into common stock at the then-applicable conversion price. The conversion price for the Note shall be equal to the Variable Conversion Price (as defined herein) (subject to equitable adjustments for stock splits, stock dividends or rights offerings by the Company relating to the Company’s securities or the securities of any subsidiary of the Company, combinations, recapitalization, reclassifications, extraordinary distributions and similar events). The "Variable Conversion Price" shall mean 65% multiplied by the Market Price (as defined herein) (representing a discount rate of 35%). "Market Price" means the average of the lowest three (3) Trading Prices (as defined below) for the common stock during the ten (10) Trading Day period ending on the latest complete Trading Day (as defined below) prior to the conversion date. "Trading Price" means, for any security as of any date, the closing bid price on the OTCQB, OTCQX, Pink Sheets electronic quotation system or applicable trading market (the "OTC") as reported by a reliable reporting service designated by Red Road (i.e. Bloomberg) or, if the OTC is not the principal trading market for such security, the closing bid price of such security on the principal securities exchange or trading market where such security is listed or traded or, if no closing bid price of such security is available in any of the foregoing manners, the average of the closing bid prices of any market makers for such security that are listed in the "pink sheets". "Trading Day" shall mean any day on which the common stock is tradable for any period on the OTC, or on the principal securities exchange or other securities market on which the common stock is then being traded. Notwithstanding the foregoing, Red Road shall be restricted from effecting a conversion if such conversion, along with other shares of the Company’s common stock beneficially owned by Red Road and its affiliates, exceeds 4.99% of the outstanding shares of the Company’s common stock.

The Note may be prepaid until 180 days from the issuance date. If the Note is prepaid within 60 days of the issuance date, then the prepayment premium shall be 110% of the face amount plus any accrued interest, if prepaid after 60 days from the issuance date, but less than 91 days from the issuance date, then the prepayment premium shall be 115% of the face amount plus any accrued interest, if prepaid after 90 days from the issuance date, but less than 121 days from the issuance date, then the prepayment premium shall be 120% of the face amount plus any accrued interest, if prepaid after 120 days from the issuance date, but less than 151 days from the issuance date, then the prepayment premium shall be 125% of the face amount plus any accrued interest, and if prepaid after 150 days from the issuance date, but less than 181 days from the issuance date, then the prepayment premium shall be 129% of the face amount plus any accrued interest. So long as the Note is outstanding, the Company covenants not to, without prior written consent from Red Road, sell, lease or otherwise dispose of all or substantially all of its assets outside the ordinary course of business which would render the Company a "shell company" as such term is defined in Rule 144.

On October 6, 2022 Knight Therapeutics Inc., (TSX: GUD) ("Knight") a pan-American (ex-USA) specialty pharmaceutical company, reported that its Brazilian affiliate, United Medical Ltd., has submitted a marketing authorization application for tafasitamab in combination with lenalidomide to ANVISA, the Brazilian health regulatory agency, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplantation (ASCT) (Press release, Knight Therapeutics, OCT 6, 2022, View Source [SID1234621837]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In September 2021, Knight entered into an exclusive supply and distribution agreement with Incyte (NASDAQ:INCY), for the exclusive rights to distribute tafasitamab (sold as Monjuvi in the United States and Minjuvi in Europe), as well as pemigatinib (Pemazyre), in Latin America.

"We are delighted to reach this key milestone for tafasitamab in Brazil," said Samira Sakhia, President and Chief Executive Officer of Knight Therapeutics. "Upon approval, combination therapy with tafasitamab and lenalidomide will be an important new therapeutic option for eligible patients with relapsed or refractory DLBCL in Brazil. We look forward to continuing to work with the support of our partner, Incyte, as we work towards regulatory submissions in additional countries in Latin America over the next year."

About Tafasitamab

Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting immunotherapy. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP).

In the United States, Monjuvi (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplantation (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In Europe, Minjuvi (tafasitamab) received conditional approval, in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplantation (ASCT).

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in several ongoing combination trials.

Minjuvi and Monjuvi are registered trademarks of MorphoSys AG. Tafasitamab is co-marketed by Incyte and MorphoSys under the brand name Monjuvi in the U.S., and marketed by Incyte under the brand name Minjuvi in Region Europe, the United Kingdom and Canada. As part of its agreement with MorphoSys, Incyte received exclusive commercialization rights for tafasitamab outside the United States.

XmAb is a registered trademark of Xencor, Inc.

On October 6, 2022 T-Cure Bioscience, Inc., a privately held company focused on developing T cell receptor (TCR) therapy products for the treatment of solid tumors, reported that the National Cancer Institute (NCI) and Rutgers University sites are open to recruit patients for the treatment of Kita-Kyushu lung cancer antigen 1 (KK-LC-1) expressing malignancies, including gastric, lung, cervical and triple negative breast cancers (Press release, T-Cure Bioscience, OCT 6, 2022, View Source [SID1234621836]). The investigator-initiated phase 1 trials are intended to evaluate the safety and tolerability with dose escalation of the autologous TCR-T cells targeting KK-LC-1. The investigators are now actively recruiting participants who have failed first-line therapy for the above-referenced solid tumors.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

T-Cure licensed the commercial rights of the KK-LC-1 TCR-T therapy and entered into a Cooperative Research and Development Agreement (CRADA) with the NCI in 2020. The Company also initiated pre-clinical and clinical studies on KK-LC-1 TCR-T with Rutgers University in 2021.

"We have been working with the principal investigator at Rutgers University, Dr. Christian Hinrichs, and the NCI, Drs. James Gulley and Scott Norberg for a couple of years. We are extremely excited to see both sites have received IND clearance from the FDA, and are now open for recruitment", stated Gang Zeng, Ph.D., Chief Executive Officer of T-Cure. "Our investigators are key opinion leaders of the cell therapy field. We are fortunate to work together to advance this novel TCR product candidate through the first ever clinical development in the world."

Patients entering the trial are selected based on their expression of the KK-LC-1 antigen as determined by an immunohistochemistry assay. This assay was developed by T-Cure and validated for use in the ongoing trials.

Of note, the KK-LC-1 TCR was isolated from the tumor-infiltrating lymphocytes of a patient who had a complete response to immunotherapy without any toxicities. KK-LC-1 is a unique target and cannot be readily targeted by antibody, chimeric antigen receptor (CAR), or antibody drug conjugate (ADC) therapies. Trials at Rutgers University and NCI (clinicaltrials.gov link) are first-in-human targeting KK-LC-1 for multiple solid tumors.

On October 6, 2022 Sanofi US reported it has entered into a co-promotion service agreement with Provention Bio, Inc., for the commercialization of teplizumab in the United States (Press release, Sanofi, OCT 6, 2022, View Source [SID1234621812]). Teplizumab, developed by Provention, is an investigational anti-CD3 monoclonal antibody that is being evaluated for the delay of clinical type 1 diabetes (T1D) in at-risk individuals, as indicated by the presence of two or more T1D-related autoantibodies. If approved by the U.S. Food and Drug Administration (FDA), teplizumab would be the first-ever disease-modifying therapy in T1D.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Pending FDA approval, Sanofi US will co-promote teplizumab along with its existing portfolio of diabetes therapies, and leverage its customer-facing field teams with the aim of accelerating uptake of teplizumab across the U.S.

Olivier Bogillot
Head of U.S. General Medicines, Sanofi
"We are delighted by the prospect of supporting Provention Bio in bringing to the U.S. what could become the first-in-class therapy to change the course of type 1 diabetes. If approved, Sanofi US will leverage our existing world-class capabilities in diabetes care to enhance efforts in both patient and healthcare provider access. We are prepared to tap into all of our internal expertise to support the successful launch of this innovative therapy."

Jason Hoitt
Chief Commercial Officer, Provention Bio
"Teplizumab represents a potentially disruptive new therapy for T1D, and we are excited to work alongside Sanofi US to bring the first-ever disease-modifying therapy, if approved, to individuals in the U.S. who are at risk of developing clinical-stage type 1 diabetes."

The FDA is expected to make a decision on the regulatory approval for teplizumab on November 17, 2022.

Agreement Terms
Dependent on a positive decision from the FDA, Provention Bio will contract Sanofi US customer-facing field teams. Provention Bio retains all rights to teplizumab, responsible for key activities such as R&D, pharmacovigilance, production, quality and safety.

As of the effective date of the service agreement, Sanofi US has committed to make an upfront payment of $20 million to Provention Bio. In connection with this transaction, Provention Bio has granted Sanofi US an exclusive right of first negotiation for a potential in-license agreement of teplizumab in T1D.

Sanofi US also has agreed to make an equity investment of $35 million in Provention Bio, within a defined period after FDA approval of teplizumab, should this take place.

About type 1 diabetes
Type 1 diabetes is a condition caused by autoimmune damage of the insulin-producing beta-cells of the pancreas. As a result of this autoimmune attack, the body produces very little or no insulin which can lead to death if the insulin is not replaced.

Living with T1D is complex. In addition to daily insulin injections or infusion via an insulin pump, people living with T1D also need to adopt a strict management plan which includes regular blood sugar monitoring, healthy diet and physical activity.