On March 9, 2020 Biocon Ltd. (BSE code: 532523, NSE: BIOCON) and Mylan N.V.(NASDAQ: MYL) reported that the U.S. Food and Drug Administration (FDA) has accepted Mylan’s Biologics License Application (BLA) for MYL-1402O, a proposed biosimilar to Avastin (bevacizumab), for review under the 351(k) pathway (Press release, Biocon, MAR 9, 2020, View Source [SID1234594758]).

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 BLA seeks approval of bevacizumab for first-line and second-line treatment of patients with metastatic colorectal cancer in combination with fluorouracil-based chemotherapy; first-line use for patients with non-squamous non-small cell lung cancer; recurrent glioblastoma; metastatic renal cell carcinoma in combination with interferon alfa; and persistent, recurrent or metastatic cervical cancer.

The FDA goal date set under the Biosimilar User Fee Act (BsUFA) is Dec. 27, 2020.

Biocon and Mylan’s proposed biosimilar bevacizumab is expected to be the third biosimilar from the partnered portfolio for the cancer patients in the U.S. It is currently available in India and other developing markets.

Dr Christiane Hamacher, CEO, Biocon Biologics, said: "The US FDA’s acceptance of our BLA for a proposed biosimilar bevacizumab co-developed by Biocon Biologics and Mylan is an important milepost in our journey of enabling access to affordable cancer therapies for patients. Once approved, our proposed biosimilar bevacizumab will provide an affordable alternative to the branded biologic for the approved indications. Biocon Biologics’ strong R&D and manufacturing capabilities have enabled us to offer two key biosimilars to cancer patients in the U.S. and bevacizumab will further expand our oncology portfolio."

Mylan President Rajiv Malik commented: "As we continue toward our goal of expanding access to cancer treatments for oncology patients, the FDA acceptance of our application for proposed biosimilar bevacizumab is another important step forward to increase competition, drive health system savings and expand our growing oncology portfolio to provide a broad range of offerings. We’re encouraged by the results of our scientific program to date and look forward to advancing the review of our application."

The BLA is supported by a global randomized, controlled phase 3 clinical trial to evaluate the efficacy, safety and immunogenicity of proposed biosimilar bevacizumab versus Avastin.

The study included patients diagnosed with stage 4 non-squamous non-small cell lung cancer. Eligible patients were randomised to receive either the proposed biosimilar bevacizumab or Avastin along with carboplatin and paclitaxel for up to six cycles (18 weeks). After which the patients continued to receive monotherapy until week 42. Additionally, patients benefitting from the treatment continued on bevacizumab monotherapy. The primary endpoint was overall response at week 18, using RECIST 1.1. Secondary endpoints included safety, progression free survival and overall survival at week 18 and 42.

A total of 671 patients were randomized. At week 18, the study met the primary endpoint and the 90% confidence interval for the best ORR (objective response rate) ratio was within the pre-specified equivalence margin. The safety which included immunogenicity was found to be similar to Avastin.

About the Biocon and Mylan Partnership
Mylan and Biocon Biologics are exclusive partners on a broad portfolio of biosimilar and insulin products. Our proposed biosimilar bevacizumab is one of the 11 biologic products being co-developed by Mylan and Biocon for the global marketplace. Mylan has exclusive commercialization rights for the product in the U.S., Canada, Japan, Australia, New Zealand and in the European Union and European Free Trade Association countries. Biocon has co-exclusive commercialization rights with Mylan for the product in the rest of the world.

On March 9, 2020 Mylan N.V. (NASDAQ: MYL) and Biocon Ltd. (BSE code: 532523, NSE: BIOCON) reported that the U.S. Food and Drug Administration (FDA) has accepted Mylan’s Biologics License Application (BLA) for MYL-1402O, a proposed biosimilar to Avastin (bevacizumab), for review under the 351(k) pathway (Press release, Mylan, MAR 9, 2020, View Source [SID1234565288]).

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 BLA seeks approval of bevacizumab for first-line and second-line treatment of patients with metastatic colorectal cancer in combination with fluorouracil-based chemotherapy; first-line use for patients with non-squamous non-small cell lung cancer; recurrent glioblastoma; metastatic renal cell carcinoma in combination with interferon alfa; and persistent, recurrent or metastatic cervical cancer.

The FDA goal date set under the Biosimilar User Fee Act (BsUFA) is Dec. 27, 2020.

Mylan and Biocon’s proposed biosimilar bevacizumab is expected to be the third biosimilar from the partnered portfolio for cancer patients in the U.S. It is currently available in India and other developing markets.

Mylan President Rajiv Malik commented: "As we continue toward our goal of expanding access to cancer treatments for oncology patients, the FDA acceptance of our application for proposed biosimilar bevacizumab is another important step forward to increase competition, drive health system savings and expand our growing oncology portfolio to provide a broad range of offerings. We’re encouraged by the results of our scientific program to date and look forward to advancing the review of our application."

Dr Christiane Hamacher, CEO, Biocon Biologics, said: "The US FDA’s acceptance of our BLA for a proposed biosimilar bevacizumab co-developed by Biocon Biologics and Mylan is an important milepost in our journey of enabling access to affordable cancer therapies for patients. Once approved, our proposed biosimilar bevacizumab will provide an affordable alternative to the branded biologic for the approved indications. Biocon Biologics’ strong R&D and manufacturing capabilities have enabled us to offer two key biosimilars to cancer patients in the U.S. and bevacizumab will further expand our oncology portfolio."

The BLA is supported by a global randomized, controlled phase 3 clinical trial to evaluate the efficacy, safety and immunogenicity of proposed biosimilar bevacizumab versus Avastin. The study included patients diagnosed with stage 4 non-squamous non-small cell lung cancer. Eligible patients were randomised to receive either the proposed biosimilar bevacizumab or Avastin along with carboplatin and paclitaxel for up to six cycles (18 weeks). After which the patients continued to receive monotherapy until week 42. Additionally, patients benefitting from the treatment continued on bevacizumab monotherapy. The primary endpoint was overall response at week 18, using RECIST 1.1. Secondary endpoints included safety, progression free survival and overall survival at week 18 and 42.

A total of 671 patients were randomized. At week 18, the study met the primary endpoint and the 90% confidence interval for the best ORR (objective response rate) ratio was within the pre-specified equivalence margin. The safety which included immunogenicity was found to be similar to Avastin.

About the Biocon and Mylan Partnership
Mylan and Biocon Biologics are exclusive partners on a broad portfolio of biosimilar and insulin products. Our proposed biosimilar bevacizumab is one of the 11 biologic products being co-developed by Mylan and Biocon for the global marketplace. Mylan has exclusive commercialization rights for the product in the U.S., Canada, Japan, Australia, New Zealand and in the European Union and European Free Trade Association countries. Biocon has co-exclusive commercialization rights with Mylan for the product in the rest of the world.

On March 9, 2020 Abbisko Therapeutics, a clinical-stage biopharmaceutical company, reported that it has received the regulatory approval by the National Medical Products Administration (NMPA) of China to initiate its phase 1 trial for ABSK-011, a novel FGFR4 inhibitor in advanced solid tumors (Press release, Abbisko Therapeutics, MAR 9, 2020, View Source;article_id=138&brd=1 [SID1234556285]).

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!

ABSK-011 is independently discovered and developed by Abbisko Therapeutics with full intellectual property rights worldwide. It is an orally administrated, highly potent, and selective small molecule inhibitor of FGFR4 with best-in-class drug-like properties. Through disruption of FGF19-FGFR4 pathway activities, ABSK-011 offers a potential novel therapeutic approach to treat cancers such liver cancers harboring aberrant FGFR4 pathway alterations. Liver cancer in China accounts for ~50% of the global incidence with poor survival rate and limited treatment options, representing a major unmet clinical needs in the territory and around the world. To date, no FGFR4-targeted therapies have been approved worldwide.

ABSK-011 is the first program of Abbisko Therapeutics to be approved for clinical studies in China. In December 2019, Abbisko has also received the IND approval in Taiwan to conduct first-in-human studies of ABSK-011.

Founded in April 2016, Abbisko Therapeutics Co., Ltd. is a biopharmaceutical company dedicated to discovering and developing innovative therapeutics to treat cancer and other diseases with unmet medical needs. The founders and core team of Abbisko are industrial veterans with strong leadership and managerial experiences from top international pharmaceutical companies. Over three years, Abbisko has established a strong oncology pipeline with multiple programs entering the clinic.

On March 9, 2020 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune diseases, reported the approval of its Investigational New Drug ("IND") application by the United States Food and Drug Administration ("FDA") for eftilagimod alpha ("efti" or "IMP321") (Press release, Immutep, MAR 9, 2020, View Source [SID1234555341]).

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 FDA approval of the IND allows Immutep to initiate its planned AIPAC-002 Phase I clinical study in metastatic breast cancer (MBC) patients. Immutep will commence the study, subject to the completion of other preparatory steps and pending positive results from its larger AIPAC Phase IIb study, which are expected to be reported by the end of March 2020.

Immutep CEO, Marc Voigt stated: "Receiving our second IND approval for efti from the FDA is a crucial step forward for Immutep. The IND allows us to initiate, effectively, a small bridging study called AIPAC-002 that enables us to further interact with the FDA in terms of efti in metastatic breast cancer. The results of our larger AIPAC trial will be reported this month. If they are positive, we will proceed with the final preparations and more importantly, will advance our discussions with regulators in order to make key strategic decisions about efti."

Overview of AIPAC-002

AIPAC-002 is a Phase I trial evaluating efti in combination with a taxane-based standard of care chemotherapy, called paclitaxel, in 24 patients with MBC in the US and the EU to boost the T-cell immune responses against tumours. This is the same combination therapy being investigated in Immutep’s Phase IIb AIPAC study. The trial forms part of Immutep’s strategy to expedite the possible use of efti for MBC patients in the US.

The IND application allows Immutep to ship efti across US state borders to US clinical investigators participating in the AIPAC-002 clinical study.

On March 9, 2020, BridgeBio Pharma, Inc. ("BridgeBio") reported an aggregate of $550.0 million aggregate principal amount of its 2.50% Convertible Senior Notes due 2027 (the "Notes"), pursuant to an Indenture dated March 9, 2020 (the "Indenture"), between BridgeBio and U.S. Bank National Association, as trustee (the "Trustee"), in a private offering to qualified institutional buyers (the "Note Offering") pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Filing, 8-K, BridgeBio, MAR 9, 2020, View Source [SID1234555340]). The Notes issued in the Note Offering include $75.0 aggregate principal amount of Notes sold to the initial purchasers in (the "Initial Purchasers") pursuant to the exercise in full of the Initial Purchasers’ option to purchase additional Notes.

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 Notes are senior, unsecured obligations of BridgeBio and will accrue interest payable semiannually in arrears on March 15 and September 15 of each year, beginning on September 15, 2020, at a rate of 2.50 % per year. The Notes will mature on March 15, 2027, unless earlier converted or repurchased. The Notes are convertible into cash, shares of BridgeBio’s common stock or a combination of cash and shares of BridgeBio’s common stock, at BridgeBio’s election.

The net proceeds BridgeBio received from the Note Offering are equal to approximately $537.0 million, after deducting the Initial Purchasers’ discount and estimated offering expenses payable by BridgeBio. BridgeBio used approximately $49.3 million of the net proceeds from the Note Offering to pay the cost of the Capped Call Transactions described below, and approximately $75.0 million to pay the cost of Repurchases of shares of its common stock described below. BridgeBio intends to use the remainder of the net proceeds from the Note Offering for working capital and other general corporate purposes, including for its commercial organization and launch preparations. BridgeBio may also use any remaining net proceeds to fund possible acquisitions of, or investments in, complementary businesses, products, services and technologies. BridgeBio has not entered into any agreements or commitments with respect to any material acquisitions or investments at this time.

A holder of Notes may convert all or any portion of its Notes at its option at any time prior to the close of business on the business day immediately preceding December 15, 2026 only under the following circumstances: (1) during any calendar quarter commencing after the calendar quarter ending on June 30, 2020 (and only during such calendar quarter), if the last reported sale price of BridgeBio’s common stock for at least 20 trading days (whether or not consecutive) during a period of 30 consecutive trading days ending on, and including, the last trading day of the immediately preceding calendar quarter is greater than or equal to 130% of the conversion price on each applicable trading day; (2) during the five business day period after any five consecutive trading day period (the "measurement period") in which the "trading price" (as defined in the Indenture) per $1,000 principal amount of Notes for each trading day of the measurement period was less than 98% of the product of the last reported sale price of BridgeBio’s common stock and the conversion rate on each such trading day; or (3) upon the occurrence of specified corporate events. On or after December 15, 2026 until the close of business on the second scheduled trading day immediately preceding the maturity date, a holder may convert all or any portion of its Notes at any time, regardless of the foregoing.

The conversion rate will initially be 23.4151 shares of BridgeBio’s common stock per $1,000 principal amount of Notes (equivalent to an initial conversion price of approximately $42.71 per share of BridgeBio’s common stock). The conversion rate is subject to adjustment in some events but will not be adjusted for any accrued and unpaid interest. In addition, following certain corporate events that occur prior to the maturity date, BridgeBio will, in certain circumstances, increase the conversion rate for a holder who elects to convert its Notes in connection with such a corporate event.

BridgeBio may not redeem the Notes prior to the maturity date, and no sinking fund is provided for the Notes.

If BridgeBio undergoes a fundamental change (as defined in the Indenture), holders may require BridgeBio to repurchase for cash all or any portion of their Notes at a fundamental change repurchase price equal to 100% of the principal amount of the Notes to be repurchased, plus any accrued and unpaid interest to, but excluding, the fundamental change repurchase date.

The Indenture contains customary terms and covenants, including that upon certain events of default occurring and continuing, either the Trustee or the holders of not less than 25% in aggregate principal amount of the Notes then outstanding may declare the entire principal amount of all the Notes plus accrued special interest, if any, to be immediately due and payable.

The Notes are BridgeBio’s general unsecured obligations and rank senior in right of payment to all of BridgeBio’s indebtedness that is expressly subordinated in right of payment to the Notes; equal in right of payment with all of BridgeBio’s liabilities that are not so subordinated; effectively junior to any of BridgeBio’s secured indebtedness to the extent of the value of the assets securing such indebtedness; and structurally junior to all indebtedness and other liabilities (including trade payables) of BridgeBio’s subsidiaries.

A copy of the Indenture and form of Note are filed as Exhibit 4.1 and Exhibit 4.2, respectively, to this Current Report on Form 8-K and are incorporated by reference herein. The foregoing description of the Indenture and Notes does not purport to be complete and is qualified in its entirety by reference to such exhibits.