On March 11, 2021 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for poziotinib for the treatment of non-small cell lung cancer (NSCLC) in previously treated patients with HER2 exon 20 mutations (Press release, Spectrum Pharmaceuticals, MAR 11, 2021, View Source [SID1234576516]). Spectrum plans to submit a new drug application (NDA) for poziotinib later this year.

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"There are currently no approved therapies to treat patients with HER2 exon 20 mutations and we are pleased that the FDA has granted Fast Track designation for poziotinib," said Joe Turgeon, President and CEO of Spectrum Pharmaceuticals. "Momentum is building to unlock the potential of poziotinib."

"We are actively preparing the NDA and delighted with this Fast Track designation," stated Francois Lebel, M.D., Chief Medical Officer of Spectrum Pharmaceuticals. "In addition, last week we presented at the European Society for Medical Oncology Targeted Anticancer Therapies (ESMO TAT) Virtual Congress 2021 that twice daily dosing (BID) suggests improved anti-tumor activity and reduced toxicity relative to once daily dosing. We are optimistic about this BID strategy and we will provide a data update at AACR (Free AACR Whitepaper) in April."

About Fast Track Designation

Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious and life-threatening conditions and fill unmet medical needs, with the intention of getting important new drugs to patients earlier. Specifically, Fast Track designation facilitates meetings with the FDA to discuss aspects of development to support licensure and provides the opportunity to submit sections of a NDA on a rolling basis as data become available. When Fast Track designation is requested later in development, available clinical data should demonstrate the potential to address an unmet medical need. Additionally, another potential benefit of Fast Track designation is priority review, which reduces the standard 10 months NDA review to six months.

On March 11, 2021 Sierra Oncology, Inc. (SRRA), a late-stage biopharmaceutical company on a quest to deliver targeted therapies that treat rare forms of cancer, reported its financial and operational results for the fourth quarter and fiscal year ended December 31, 2020 (Press release, Sierra Oncology, MAR 11, 2021, View Source [SID1234576515]).

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"We are excited to enter the final phase of patient recruitment for MOMENTUM. Trial enrollment remains on track, and we anticipate closing screening in the first half of the year," said Stephen Dilly, MBBS, PhD, President and CEO of Sierra Oncology. "Two important retrospective analyses from the SIMPLIFY studies were presented in December 2020 at the American Society of Hematology (ASH) (Free ASH Whitepaper). Long-term survival in both JAK inhibitor-naïve and JAK inhibitor-exposed patients highlighted momelotinib’s disease modifying potential, and, efficacy in patients with reduced platelets added to the totality of evidence supporting momelotinib’s unique and differentiated profile.

"We are now looking forward to completing enrollment of our pivotal Phase 3 MOMENTUM study, analyzing and presenting topline data, and preparing internally for commercialization. Results of the MOMENTUM study, combined with the SIMPLIFY data sets, will support future regulatory filings and the potential approval of momelotinib for the treatment of myelofibrosis."

Recent and Upcoming Business Highlights

Pivotal Phase 3 MOMENTUM study is on track to complete enrollment by mid-2021. Top-line data are anticipated in H1 2022
Following top-line data availability, Sierra anticipates filing for regulatory approval of momelotinib in H2 2022
Robust overall survival and sustained efficacy outcome data from the previously completed SIMPLIFY studies presented at American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2020
Long-term safety and dose intensity data presented at European Hematology Association (EHA) (Free EHA Whitepaper) annual meeting in June 2020
Significant executive appointments made in preparation for commercial execution: Chief Executive Officer, Stephen Dilly, Chief Business Officer, Kevin Norrett, General Counsel, Christina Thomson and Chief Regulatory & Technical Operations Officer, William Turner
Amendment to CRT Pioneer Fund agreement for SRA737 allowing for potential future development of the compound
Year End 2020 Financial Results (all amounts reported in U.S. currency)
Research and development expenses were $45.1 million for the year ended December 31, 2020 compared to $53.2 million for the year ended December 31, 2019. The decrease was primarily due to a non-cash charge of $10.5 million that was recognized during the year ended December 31, 2019 pertaining to an obligation to issue common stock and a warrant to Gilead Sciences, Inc. (Gilead) in consideration for meaningfully reduced royalty rates and the elimination of a milestone payment, partially offset by a $1.5 million non-cash charge during the year ended December 31, 2020 to recognize the change in fair value of the securities until their issuance in January of 2020. Also contributing to the decrease was a reduction of $7.6 million in clinical trial, third-party manufacturing, and research and preclinical costs for SRA737 and a $0.9 million decrease in personnel-related and allocated overhead costs for the year ended December 31, 2020. These decreased costs were offset by a $9.4 million increase in clinical trial and development costs related to momelotinib for the year ended December 31, 2020. Research and development expenses included non-cash stock-based compensation of $4.3 million and $3.9 million for the year ended December 31, 2020 and 2019, respectively.

General and administrative expenses were $20.1 million for year ended December 31, 2020, compared to $13.7 million for the year ended December 31, 2019. The increase was due to a $4.9 million increase in personnel-related and allocated overhead costs, including a $3.4 million increase in non-cash stock-based compensation and $1.0 million of severance charges that were primarily related to the resignation of an executive, and an increase of $1.5 million in professional fees primarily relating to pre-commercial planning costs for momelotinib. General and administrative expenses included non-cash stock-based compensation of $5.2 million and $1.8 million for the year ended December 31, 2020 and 2019, respectively.

Total other income (expense), net was $15.8 million of other expense, net for the year ended December 31, 2020, compared to $21.4 million of other expense, net for the year ended December 31, 2019. The difference was primarily attributable to a non-cash charge of $20.9 million recognized during the year ended December 31, 2019, related to the change in fair value of warrant liabilities and $1.3 million of offering expenses pertaining to the issuance of the warrants in the 2019 public offering, offset by a non-cash charge of $16.2 million recognized during the year ended December 31, 2020, related to the change in fair value of warrant liabilities which were reclassified to equity in January 2020.

For the year ended December 31, 2020, Sierra incurred a Generally Accepted Accounting Principles (GAAP) net loss of $80.9 million compared to a GAAP net loss of $88.3 million for the year ended December 31, 2019. The GAAP net loss includes a non-cash charge of $16.2 million and $20.9 million, related to the change in fair value of warrant liabilities, for the year ended December 31, 2020 and December 31, 2019, respectively, and a non-cash charge of $1.5 million and $10.5 million pertaining to the obligation to issue securities to Gilead for the year ended December 31, 2020 and 2019, respectively.

Non-GAAP adjusted net loss was $53.7 million for the year ended December 31, 2020, compared with a non-GAAP adjusted net loss of $51.2 million for the year ended December 31, 2019. Non-GAAP adjusted net loss excludes expenses related to the change in fair value of warrant liabilities, the securities issuance obligation, and stock-based compensation. See "Non-GAAP Financial Measures" and "Reconciliation of GAAP to Non-GAAP Financial Measures" below for a reconciliation of this GAAP and non-GAAP financial measure.

Cash and cash equivalents totaled $104.1 million as of December 31, 2020, compared to $147.5 million as of December 31, 2019.

As of December 31, 2020, there were 11,128,484 total shares of common stock outstanding and warrants to purchase 11,102,251 shares of common stock, with an exercise price equal to $13.20 per share. There were 4,146,928 shares issuable upon exercise of stock options and an additional warrant to purchase 1,839 shares.

On March 11, 2021 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage precision oncology company focused on developing targeted therapies to inhibit frontier targets in RAS-addicted cancers, reported the company will make six presentations at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 being held April 10-15, 2021 in a virtual format (Press release, Revolution Medicines, MAR 11, 2021, View Source [SID1234576514]).

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Details of the planned presentations are as follows:

Oral Presentation:

Title: Anti-tumor activity and tolerability of the SHP2 inhibitor RMC-4630 as a single agent in patients with RAS-addicted solid cancers
Abstract Number:
LB001
Session: Late-Breaking Minisymposium 1
Date/Time: April 10, 2021 at 2:05 p.m. Eastern
Poster Presentations:

Title: First-in-class, orally bioavailable KRASG12V(ON) tri-complex inhibitors, as single agents and in combinations, drive profound anti-tumor activity in preclinical models of KRASG12V mutant cancers
Abstract Number: 1260
Session: Novel Antitumor Agents
Date/Time: April 10, 2021 at 8:30 a.m. Eastern

Title: A next generation tri-complex KRASG12C(ON) inhibitor directly targets the active, GTP-bound state of mutant RAS and may overcome resistance to KRASG12C(OFF) inhibition
Abstract Number: 1261
Session: Novel Antitumor Agents
Date/Time: April 10, 2021 at 8:30 a.m. Eastern

Title: Discovery of a potent, selective, and orally bioavailable SOS1 inhibitor, RMC-023, an in vivo tool compound that blocks RAS activation via disruption of the RAS-SOS1 interaction
Abstract Number:
1273
Session: Novel Antitumor Agents
Date/Time: April 10, 2021 at 8:30 a.m. Eastern

Title: Modulation of innate and adaptive immunity in blood and tumor of patients receiving the SHP2 inhibitor RMC-4630
Abstract Number: LB050
Session: Immune Response to Therapies
Date: April 10, 2021 at 8:30 a.m. Eastern

Title: Confirmation of target inhibition and anti-tumor activity of the SHP2 inhibitor RMC-4630 via longitudinal analysis of ctDNA in a phase 1 clinical study
Abstract Number: LB054
Session: Liquid Biopsies: Circulating DNA
Date: April 10, 2021 at 8:30 a.m. Eastern
Additional information on the AACR (Free AACR Whitepaper) Annual Meeting 2021 is available through the AACR (Free AACR Whitepaper) website at: View Source

On March 11, 2021 Replimune Group, Inc. (Nasdaq: REPL), a biotechnology company developing oncolytic immuno-gene therapies derived from its Immulytic platform, reported two poster presentations at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 being held virtually April 10-15, 2021 and May 17-21, 2021 (Press release, Replimune, MAR 11, 2021, View Source [SID1234576513]).

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Details of the presentations are as follows:

Abstract Title: Clinical biomarker studies with two fusion-enhanced versions of oncolytic HSV (RP1 and RP2) alone and in combination with nivolumab in cancer patients indicate potent immune activation
Abstract Number: LB180
Session Title: Vaccines
Session Date and Time: Saturday, April 10, 2021 at 8:30 am EDT

Abstract Title: Immunomodulatory effects of a novel, enhanced potency gibbon ape leukemia virus (GALV) fusogenic membrane glycoprotein-expressing herpes simplex virus platform with increased efficacy combined with anti PD-1 therapy
Abstract Number: 1917
Session Title: Vaccines
Session Date and Time: Saturday, April 10, 2021 at 8:30 am EDT
This is a collaborative presentation between Replimune and the Institute of Cancer Research, London, UK.

The abstract for poster LB180 is embargoed until 12:01 a.m. ET on April 9, 2021. The abstract for poster 1917 is currently available at View Source Both full posters will be available for on-demand viewing on the AACR (Free AACR Whitepaper) Annual Meeting 2021 website starting at 8:30 am ET on April 10, 2021 and will also be posted to the presentations section of the Replimune website at View Source

On March 11, 2021 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage biopharmaceutical company utilizing proprietary genetic engineering platform technologies to create cell and gene therapeutics with the capacity to cure, reported program updates and financial results for the fourth quarter and full year ended December 31, 2020 (Press release, Poseida Therapeutics, MAR 11, 2021, View Source [SID1234576512]).

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"2020 was a transformative year for Poseida, as we completed our IPO and became a public company all while advancing multiple programs and substantially expanding the application of our core technologies, enabling us to engineer a portfolio of product candidates designed to overcome the limitations of current cell and gene therapeutics," said Eric Ostertag, M.D., Ph.D., Chief Executive Officer of Poseida. "This important progress was on display in late February, when we hosted our first R&D Day, showcasing the wide breadth of our capacity in cell and gene therapies and introducing a potential new product candidate for the in vivo treatment of hemophilia A to our gene therapy pipeline. We look forward to achieving important milestones in 2021 as we continue to move our programs and platform forward."

Program Updates

BCMA Program
P-BCMA-101 is an autologous CAR-T product candidate in an ongoing Phase 1 dose expansion trial and Phase 2 trial in development for the treatment of relapsed/refractory multiple myeloma. The Company provided an update on the P-BCMA-101 program during an oral presentation at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on December 5, 2020. The interim results showed that patients treated with equivalent doses of product manufactured with a modified nanoplasmid process in the expanded Phase 1 trial achieved increases in the depth and rate of responses while maintaining the potentially best-in-class P-BCMA-101 safety profile seen with product manufactured with the Company’s legacy plasmid. Additionally, at the Company’s R&D Day, patient case studies were presented that clinically demonstrated the value of products with a high percentage of stem cell memory T cells (Tscm), potentially leading to better duration of response and the ability to re-respond to relapse without re-administration of product. Phase 1 dose expansion enrollment continues, with an expected update on this program later in 2021.

P-BCMA-ALLO1, the Company’s first allogeneic CAR-T product candidate, is in development for the treatment of relapsed/refractory multiple myeloma and is designed to be fully allogeneic, with genetic edits designed to reduce or eliminate both host-vs-graft and graft-vs-host alloreactivity. The program is proceeding toward an IND filing, which is expected in the first half 2021.

PSMA Program
P-PSMA-101 is a solid tumor autologous CAR-T product candidate being developed to treat patients with metastatic castrate resistant prostate cancer (mCRPC) currently in an ongoing Phase 1 dose escalation trial. The Company’s R&D Day included a case study of a patient with mCRPC treated with P-PSMA-101 in the low dose cohort of 0.25 x 10e6 cells/kg (~20 x 10e6 total cells) who showed a marked decrease in prostate specific antigen (PSA) expression levels of more than 50% in the first three weeks post treatment and is continuing on trial. The patient was reported to have Grade 1 CRS in the second week which was treated to resolution. The Company intends to provide an additional update on this program later in 2021.

MUC1-C Program
P-MUC1C-ALLO1 is an allogeneic CAR-T product candidate in preclinical development with the potential to treat a wide range of solid tumors, including breast and ovarian cancers. P-MUC1C-ALLO1 is proceeding, with an anticipated IND filing and initiation of Phase 1 clinical trial by the end of 2021.

Liver Directed Gene Therapy Programs
P-OTC-101 is the Company’s first liver-directed gene therapy program for the in vivo treatment of urea cycle disease caused by congenital mutations in the ornithine transcarbamylase (OTC) gene, a condition characterized by high unmet medical need. The program is progressing and the Company expects an IND submission and initiation of a Phase 1 clinical trial in 2022.

P-FVIII-101, a liver directed gene therapy currently in development for the in vivo treatment of hemophilia A, was introduced at the Company’s R&D Day. P-FVIII-101 utilizes piggyBac gene modification delivered via lipid nanoparticle, resulting in stable and sustained Factor VIII expression in animal models. Preclinical studies are ongoing that will inform the development plan and timeline to IND.

Platforms and Emerging Discovery Programs
At the R&D Day, the Company also reviewed its core platform technologies and introduced a number of emerging discovery programs. The presentation is currently available on the Company’s website and included discussions on the following:

TCR-T: This platform combines the Company’s technologies to generate effective and functional off-the-shelf TCR-T product candidates with a high percentage of highly desirable Tscm cells.
Anti-cKit CAR-T: Non-genotoxic conditioning regimens that are safer than the current standard of care are potentially possible with the Company’s anti-cKit CAR-T program for hematopoietic stem cell (HSC) conditioning.
Genetically Modified HSCs: HSCs can be modified via the piggyBac DNA Delivery System and/or the Cas-CLOVER Site-Specific Gene Editing System. CAR-HSC has the potential to be a highly effective CAR-T approach.
iPSCs: The Cas-CLOVER System is efficient for creating knock-outs and knock-ins in induced pluripotent stem cells (iPSCs).
Genetically Modified NK Cells: Cas-CLOVER can also be used to efficiently edit natural killer (NK) cells, or CAR-NK cells, while piggyBac can be used to effectively deliver large therapeutic transgenes to activated or un-activated peripheral blood NK cells.
For discovery programs, the Company may seek partnerships or collaborations to move those applications forward in the near term.

Financial Results for the Fourth Quarter and Full Year 2020

Research and Development Expenses
Research and development expenses were $27.9 million for the fourth quarter ended December 31, 2020, compared to $19.2 million for the same period in 2019. For the full year ended December 31, 2020, research and development expenses were $103.5 million, compared to $60.4 million for the same period in 2019. The increase in both periods was primarily due to increased headcount, external costs related to preclinical programs and clinical stage programs, including the ongoing enrollment and manufacturing associated with our P-BCMA-101 and P-PSMA-101 clinical trials, and internal costs related to facilities development.

General and Administrative Expenses
General and administrative expenses were $7.5 million for the fourth quarter ended December 31, 2020, compared to $4.0 million for the same period in 2019. General and administrative expenses were $23.0 million for the full year ended December 31, 2020, compared to $18.5 million for the same period in 2019. The increase in both periods was primarily due to increased headcount and professional fees associated with becoming a publicly traded company.

Net Losses
Net losses were $129.8 million and $86.5 million for the full year ended December 31, 2020 and 2019, respectively.

Cash Position
As of December 31, 2020, cash, cash equivalents and marketable securities were $309.2 million.