On March 2, 2020 BridgeBio Pharma, Inc. (NASDAQ: BBIO), a clinical-stage biopharmaceutical company focused on genetic diseases, reported its fourth quarter and full year 2019 financial results and recent progress across its portfolio, which now includes more than 20 drug development and discovery programs (Press release, BridgeBio, MAR 2, 2020, View Source [SID1234555041]).

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2019 was a year of significant growth and milestone achievements for BridgeBio. The company initiated its first New Drug Application (NDA) with the United States Food and Drug Administration (FDA) and added five new drug development and discovery programs to its pipeline, which target diseases in endocrinology, ophthalmology, otology, neurology and musculoskeletal therapeutic areas. Veteran biotech and pharmaceutical industry leaders joined BridgeBio’s board of directors and the company as senior leaders, including the recent board appointment of Ronald J. Daniels, president of Johns Hopkins University. The company went public on June 27, 2019 and raised approximately $401 million in gross proceeds in its initial public offering.

"BridgeBio was founded nearly five years ago on the back of two big ideas: that there had to be a better way to finance critical biomedical research and that there was a tremendous amount of medical innovation that was trapped, without a way to move into the clinic where it could help patients," said BridgeBio founder and CEO Neil Kumar, Ph.D. "Today BridgeBio has more than 20 drug development and discovery programs in our pipeline. We initiated our first new drug application with the FDA and we are on track to file our second later this year, along with the anticipated filing of multiple investigational new drug applications. We are demonstrating that our model is working and has the potential to produce an array of life-changing therapies for people in need."

Pipeline growth:

We recently disclosed five new genetic medicine product candidates in the pipeline:

Encaleret – Calcium sensing receptor antagonist for autosomal dominant hypocalcemia type 1 (ADH1): IND application for the treatment of ADH1 became effective in late 2019; Phase 2 ready

Zuretinol – Synthetic retinoid for inherited retinal disease due to RPE65 or LRAT gene mutations: Phase 2/3 study initiating in 2020

BBP-418 – Substrate supplementation therapy for limb-girdle muscular dystrophy type 2i (LGMD2i)

BBP-472 – Brain-permeable inhibitor of PI3KB for children with autism-spectrum disorders (ASD) characterized by loss of the PTEN protein. This program is in preclinical development.

BBP-815 – AAV gene therapy for nonsyndromic hearing loss caused by recessive mutations in the TMC1 gene. This program is undergoing early proof of concept animal studies.

Fourth quarter 2019 and recent pipeline progress:

Mendelian

Low-dose infigratinib—FGFR1-3 inhibitor for achondroplasia: Initiated clinical program consisting of an observational study (PROPEL, NCT04265651) and Phase 2 dose-ranging study (PROPEL2, NCT04265651) in children with achondroplasia, the most common form of genetic short stature.

Fosdenopterin – cPMP replacement therapy for MoCD type A: Initiated a rolling submission of an NDA with the United States FDA for the treatment of patients with molybdenum cofactor deficiency (MoCD) type A.

Topical patidegib gel for Gorlin syndrome and high-frequency basal cell carcinoma1: Completed enrollment of pivotal Phase 3 clinical trial in patients with Gorlin Syndrome (NCT03703310) and initiated Phase 2 study in high-frequency basal cell carcinoma (NCT04155190).

BBP-265 (AG10) – TTR stabilizer for ATTR: Presented positive data from Phase 2 Open Label Extension (NCT03536767) in transthyretin amyloid cardiomyopathy at the American Heart Association’s 2019 Scientific Sessions.

Targeted Oncology

Infigratinib – FGFR1-3 inhibitor for FGFR+ cancer: Received FDA Fast Track Designation in adults with first-line advanced or metastatic cholangiocarcinoma and Orphan Drug Designation for the treatment of cholangiocarcinoma, and initiated Phase 3 study in advanced 1L cholangiocarcinoma as a first-line therapy (PROOF trial, NCT03773302).

BBP-398 – SHP2 inhibitor for treatment-resistant cancer: Presented data (link to poster) highlighting the discovery and preclinical activity of our potent and selective SHP2 inhibitor potentially both as monotherapy and in combination with approved agents.

Gene Therapy

BBP-812 – Gene therapy candidate for Canavan disease: Opened a natural history study in Canavan disease (treatcanavan.com) and presented preclinical data (link to poster) demonstrating intravenous (IV) dosing of BridgeBio’s experimental therapy for Canavan disease (BBP-812) achieved broad central nervous system delivery.

BBP-631 – Gene therapy candidate for CAH: Presented preclinical update (link to poster) for gene therapy candidate BBP-631 in congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency wherein IV dosing of non-human primates with BBP-631 resulted in durable delivery and expression of the gene product to the adrenal tissue.

PellePharm, which is focused on developing patidegib topical gel, 2% entered into a strategic collaboration with LEO Pharma in November 2018, which includes an option for LEO Pharma to acquire PellePharm.

Upcoming milestones:

Anticipate disclosing additional new product candidates and filing multiple new INDs in 2020

BBP-589 – COL7A protein replacement therapy for recessive dystrophic epidermolysis bullosa: Plan to share topline data from the ongoing Phase 1/2 study (NCT03752905) in 2020.

Low-dose infigratinib – FGFR1-3 inhibitor for achondroplasia: Anticipate dosing of first child in Phase 2 dose-ranging study (PROPEL2) in the coming months.

BBP-265 (AG10) – TTR stabilizer for ATTR: On track to complete enrollment in the Phase 3 study of AG10 in ATTR-CM in 2H20 (ATTRibute-CM). A Phase 3 study of AG10 in ATTR-PN (ATTRibute-PN) is on track to begin in 1H20.

Encaleret – Calcium sensing receptor antagonist for autosomal dominant hypocalcemia type 1 (ADH1): Phase 2b ready.

Infigratinib – FGFR1-3 inhibitor for FGFR+ cancer: Plan to present updated results at a major oncology meeting in 2020. Remain on track to submit new drug application for FDA approval in cholangiocarcinoma in 2020. Plan to dose first patients in a Phase 3 study in FGFR3+ adjuvant urothelial carcinoma (NCT04197986) and a Phase 2 tumor-agnostic study in patients with fusions or activating mutations in the FGFR1, 2 or 3 genes in 2020.

Organizational Growth:

Ronald J. Daniels, board member: President of Johns Hopkins University joined board of directors.

Jennifer Cook, board member and senior advisor: Genentech veteran who led Roche Pharma’s European commercial business joined board of directors and serves as a special advisor to BridgeBio.

Eli Wallace, chief scientific officer in residence for oncology: Medicinal chemist and strategic executive leader who oversaw entire research organizations at companies such as Peloton Therapeutics and Array BioPharma joined BridgeBio to lead oncology research.

Fourth quarter and full-year 2019 financial results:

Cash, Cash Equivalents and Marketable Securities

Cash, cash equivalents and marketable securities, excluding restricted cash, totaled $577.1 million as of December 31, 2019 compared with $436.1 million at December 31, 2018.

License revenue

License revenue for the fourth quarter of 2019 was $13.8 million and for the full year 2019 was $40.6 million. The full year 2019 revenue was comprised mainly of the upfront payment recognized by our subsidiary company, Eidos Therapeutics, Inc. upon execution of its License Agreement with Alexion Pharmaceuticals, Inc.

Operating Expenses

Operating expenses for the fourth quarter of 2019 were $92.5 million, as compared to $65.6 million for the same period in the prior year. The increase in operating expenses of $26.9 million was primarily attributable to increase in headcount and external-related costs to support the growth of our operations.

Full year 2019 operating expenses were $306.8 million, as compared to $183.7 million for the full year in 2018. The increase of $123.1 million was mainly due to the increase in external-related costs to support the progression in our research and development programs and growth of our operations as well as increase in headcount.

Other Income (Expense), Net

Other income (expense), net for the fourth quarter of 2019 was ($5.5) million, as compared to $16.3 million for the same period in 2018. The change of $21.8 million was primarily attributable to a gain of $19.3 million that we recognized on deconsolidation of our controlled variable interest entity, PellePharm, Inc. in 2018.

Other income (expense), net for the full year 2019 was ($22.3) million, as compared to $14.2 million for the full year in 2018. The change of $36.5 million was primarily attributable to an increase in our net loss of equity method investments by $20.9 million in 2019 and the gain of $19.3 million on deconsolidation of our controlled variable interest entities, PellePharm, Inc.

Upon the closing of our IPO on July 1, 2019, we completed a reorganization (the "Reorganization"), whereby all unitholders of BridgeBio Pharma LLC, our predecessor entity ("BBP LLC") exchanged their units for shares of common stock of BridgeBio Pharma, Inc. (the "Corporation"), and BBP LLC became a wholly-owned subsidiary of the Corporation. Subsequent to the Reorganization, as the sole managing member, BridgeBio operates and controls all of BBP LLC’s businesses and affairs. The condensed consolidated financial statements as of and for the year ended December 31, 2018 are derived from the audited consolidated financial statements as of that date and were retroactively adjusted, including shares and per share amounts, as a result of the Reorganization. See the BridgeBio Pharma, Inc. Registration Statement on Form S-1 (File No. 333-231759) for additional details.

December 31, 2019 amount includes long-term marketable securities of $31.1 million.

On March 2, 2020 VBL Therapeutics (Nasdaq: VBLT), a clinical-stage biotechnology company focused on the discovery, development and commercialization of first-in-class treatments for cancer, reported that it will host a conference call and live audio webcast on Thursday, March 19 at 8:30am Eastern Time to report fourth quarter and year ended December 31, 2019 financial results and to provide a corporate update (Press release, VBL Therapeutics, MAR 2, 2020, View Source [SID1234555040]).

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Thursday March 19th @ 8:30amET
From the US: 877-407-9208
International: 201-493-6784
Conference ID: 13699636
Webcast: View Source

On March 2, 2020 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported that senior management will present at two upcoming investor conferences (Press release, Ligand, MAR 2, 2020, View Source [SID1234555039]).

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Management will deliver a company presentation at the Barclays Global Healthcare Conference on Tuesday, March 10th at 2:35 p.m. ET taking place in Miami Beach, FL.
Management will deliver a company presentation at the 32nd Annual Roth Conference on Monday, March 16th at 1:30 p.m. ET taking place in Dana Point, CA.
The audio portion of the presentations will be available on the Investors page of the Ligand Pharmaceuticals website at View Source

On March 2, 2020 Heron Therapeutics, Inc. (Nasdaq: HRTX), a commercial-stage biotechnology company focused on improving the lives of patients by developing best-in-class treatments to address some of the most important unmet patient needs, reported financial results for the three and twelve months ended December 31, 2019 and highlighted recent corporate updates (Press release, Heron Therapeutics, MAR 2, 2020, View Source [SID1234555028]).

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Recent Corporate Updates

Pain Management Franchise

New Drug Application for HTX-011: In September 2019, Heron resubmitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for HTX-011, an investigational agent for the management of postoperative pain. In February 2020, Heron announced that the FDA has extended the review period for the NDA for HTX-011 by up to three months. The new Prescription Drug User Fee Act (PDUFA) goal date is June 26, 2020.

Contract Manufacturing Site for HTX-011: In February 2020, Heron announced that the contract manufacturing site used to manufacture HTX-011 has been reinspected by the FDA with no Form 483 observations issued and with a recommendation by the FDA inspector for approval of the site. Heron has not been informed of any other manufacturing concerns.

Marketing Authorisation Application for HTX-011 in the European Union: In March 2019, Heron’s Marketing Authorisation Application (MAA) for HTX-011 for the management of postoperative pain was validated by the European Medicines Agency (EMA) for review under the Centralised Procedure. An opinion from the EMA’s Committee for Medicinal Products for Human Use (CHMP) is anticipated in the second quarter of 2020.

New Drug Submission for HTX-011 in Canada: In December 2019, Heron’s New Drug Submission (NDS) for HTX-011 for the management of postoperative pain was granted Priority Review status and accepted by Health Canada. Health Canada’s Priority Review status provides an accelerated 6-month review target for the NDS. A decision by Health Canada is anticipated in the third quarter of 2020.

CINV Franchise

CINV 2019 Net Product Sales: For the three months ended December 31, 2019, chemotherapy-induced nausea and vomiting (CINV) franchise net product sales were $35.1 million, up 22% from the same period in 2018. For the twelve months ended December 31, 2019, CINV franchise net product sales were $146.0 million, up 88% from the same period in 2018.

CINVANTI Net Product Sales: Net product sales of CINVANTI (aprepitant) injectable emulsion for the three and twelve months ended December 31, 2019 were $34.6 million and $132.2 million, respectively, compared to $23.4 million and $56.2 million, respectively, for the same periods in 2018.

SUSTOL Net Product Sales: Net product sales of SUSTOL (granisetron) extended-release injection for the three and twelve months ended December 31, 2019 were $0.5 million and $13.8 million, respectively, compared to $5.4 million and $21.3 million for the same periods in 2018. On October 1, 2019, the Company made a business decision to discontinue all discounting of SUSTOL, which resulted in significantly lower SUSTOL net product sales.

2020 Net Product Sales Guidance: Heron expects 2020 net product sales for the CINV franchise of $70 million to $80 million and the CINV franchise to return to growth in 2021 and beyond.

"We have made important advances in 2019 in both our pain management and CINV franchises, highlighted by the advancement of HTX-011 toward marketing approvals and strong sales for our CINV franchise," said Barry Quart, Pharm.D., President and Chief Executive Officer of Heron Therapeutics. "We look forward to launching HTX-011 for postoperative pain management in the second half of 2020, pending FDA approval."

Financial Results

Net product sales for the three and twelve months ended December 31, 2019 were $35.1 million and $146.0 million, respectively, compared to $28.8 million and $77.5 million, respectively, for the same periods in 2018.

Heron’s net loss for the three and twelve months ended December 31, 2019 was $57.9 million and $204.7 million, or $0.65 per share and $2.50 per share, respectively, compared to $49.6 million and $178.8 million, or $0.63 per share and $2.44 per share, respectively, for the same periods in 2018. Net loss for the three and twelve months ended December 31, 2019 included non-cash, stock-based compensation expense of $11.1 million and $51.4 million, respectively, compared to $9.8 million and $33.4 million, respectively, for the same periods in 2018.

As of December 31, 2019, Heron had cash, cash equivalents and short-term investments of $391.0 million compared to $332.4 million as of December 31, 2018. Net cash used for operating activities for the twelve months ended December 31, 2019 was $124.6 million, compared to $191.8 million for the same period in 2018. Heron expects that its current cash, cash equivalents and short-term investments will be sufficient to fund its operations into 2022.

About HTX-011 for Postoperative Pain

HTX-011, an investigational agent, is a dual-acting, fixed-dose combination of the local anesthetic bupivacaine with a low dose of the nonsteroidal anti-inflammatory drug meloxicam. It is the first and only extended-release local anesthetic to demonstrate in Phase 3 studies significantly reduced pain and opioid use through 72 hours compared to bupivacaine solution, the current standard-of-care local anesthetic for postoperative pain control. HTX-011 was granted Fast Track designation from the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2017 and Breakthrough Therapy designation in the second quarter of 2018. Heron submitted a New Drug Application (NDA) to the FDA for HTX-011 in October of 2018 and received Priority Review designation in December of 2018. A Complete Response Letter (CRL) was received from the FDA regarding the NDA for HTX-011 on April 30, 2019 relating to chemistry, manufacturing and controls and non-clinical information. No issues related to clinical efficacy or safety were noted. Heron resubmitted an NDA to the FDA for HTX-011 in September 2019. The Prescription Drug User Fee Act (PDUFA) goal date is June 26, 2020. A Marketing Authorisation Application (MMA) for HTX-011 was validated by the European Medicines Agency (EMA) in March 2019 for review under the Centralised Procedure. Heron’s New Drug Submission (NDS) for HTX-011 for the management of postoperative pain was granted Priority Review status by Health Canada in October 2019 and accepted by Health Canada in November 2019.

About CINVANTI (Aprepitant) Injectable Emulsion

CINVANTI, in combination with other antiemetic agents, is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin as a single-dose regimen, delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) as a single-dose regimen, and nausea and vomiting associated with initial and repeat courses of MEC as a 3-day regimen. CINVANTI is an IV formulation of aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist (RA). CINVANTI is the first IV formulation to directly deliver aprepitant, the active ingredient in EMEND capsules. Aprepitant (including its prodrug, fosaprepitant) is the only single-agent NK1 RA to significantly reduce nausea and vomiting in both the acute phase (0–24 hours after chemotherapy) and the delayed phase (24–120 hours after chemotherapy). The FDA-approved dosing administration included in the United States prescribing information for CINVANTI is a 30-minute IV infusion or a 2-minute IV injection.

About SUSTOL (Granisetron) Extended-Release Injection

SUSTOL is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. SUSTOL is an extended-release, injectable 5-HT3 receptor antagonist that utilizes Heron’s Biochronomer drug delivery technology to maintain therapeutic levels of granisetron for ≥5 days. The SUSTOL global Phase 3 development program was comprised of two, large, guideline-based clinical studies that evaluated SUSTOL’s efficacy and safety in more than 2,000 patients with cancer. SUSTOL’s efficacy in preventing nausea and vomiting was evaluated in both the acute phase (0–24 hours after chemotherapy) and delayed phase (24–120 hours after chemotherapy).

On March 2, 2020 Unum Therapeutics Inc. (NASDAQ: UMRX), a biopharmaceutical company focused on developing curative cell therapies for solid tumors, reported plans to prioritize resources towards advancing its preclinical program, BOXR1030, for the treatment of solid tumor cancers (Press release, Unum Therapeutics, MAR 2, 2020, View Source [SID1234555027]). Unum’s BOXR1030 expresses a glypican-3 (GPC3) targeted CAR and incorporates the novel transgene glutamic-oxaloacetic transaminase 2 (GOT2) to improve T cell function in the solid tumor microenvironment by enhancing T cell metabolism. Unum has initiated formal preclinical development activities, including preclinical safety testing and GMP process development, to support filing an IND application for BOXR1030 in late 2020.

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As part of this effort, and to conserve resources for BOXR1030, Unum is concluding its ACTR707 clinical trials, including the Phase 1 trial (ATTCK-20-03) in combination with rituximab in relapsed/refractory non-Hodgkin lymphoma and the Phase 1 trial (ATTCK-34-01) in combination with trastuzumab to treat advanced HER2+ solid tumor cancers. In addition, the company plans to reduce its current workforce by 43 employees (approximately 60 percent) to focus efforts on the BOXR1030 program. Unum also announced today that its Chief Scientific Officer, Seth Ettenberg, Ph.D., has resigned after five years of service in this role to the company. Unum expects to continue to leverage its BOXR discovery platform, potentially in collaboration with partners, to create and develop new BOXR product candidates to address a broad range of solid tumor cancers.

"Following a detailed review of our operations, opportunities, and cash reserves, we believe the decisions announced today are in the best interests of all Unum stakeholders, including patients, clinicians, employees and shareholders," said Chuck Wilson, Ph.D., President and Chief Executive Officer of Unum Therapeutics. "We remain committed to addressing the challenges of treating solid tumor cancers, and would like to thank the patients, their families, and the investigators who have made our efforts to date possible. In addition, we would like to thank Seth for his contributions to the preclinical discovery efforts here at Unum over the years and wish him the very best in his next endeavor."

Unum will provide severance, continuation of employee benefits and outplacement assistance to employees affected by the restructuring. As of September 30, 2019, Unum had cash and cash equivalents of $45.9 million. After implementation of this restructuring, Unum’s expects its current cash and cash equivalents to fund the company into mid-2021. Further details on the financial implications of the restructuring will be included in the company’s full-year 2019 results expected later this month and with related filings with the Securities and Exchange Commission.

About Unum’s BOXR1030 and BOXR Platform

Unum’s BOXR1030 was discovered from its Bolt-on Chimeric (BOXR) platform that is designed to discover novel "bolt-on" transgenes to be co-expressed with CARs, a T-cell receptor, or ACTR, to help T cells survive longer and perform better in the solid tumor microenvironment. BOXR candidates consist of two main components: 1) a targeting receptor that directs the T cell to attack tumor cells, which may be a traditional CAR receptor, a T-cell receptor, or Unum’s ACTR receptor, and 2) a novel "bolt-on" transgene that improves the intrinsic function of the T cell. Once discovered, BOXR transgenes are designed to be incorporated into several different types of therapeutic T cells, including both ACTR T cells and CAR-T cells, to impart new functionality to T cells.

Unum’s first product candidate selected from the BOXR platform, BOXR1030, expresses GPC3+ targeted CAR and incorporates the bolt-on GOT2 transgene to improve T cell function in the solid tumor microenvironment (TME) by enhancing T cell metabolism. Preclinical data with BOXR1030 was presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in November 2019. In preclinical studies, BOXR1030 T cells were resistant to suppressive TME-like conditions, showing improved T cell proliferation under both hypoxic and low glucose conditions compared with control GPC3+ CAR-T cells. In vivo, BOXR1030 demonstrated superior activity compared to the parental CAR-T with treated animals achieving complete tumor regressions. Tumor infiltrating lymphocytes isolated from the tumors of treated animals revealed that BOXR1030 cells were more resistant to dysfunction and had fewer markers of exhaustion as compared to the control CAR-T cells.