On November 6, 2019 Geron Corporation (Nasdaq: GERN) reported financial results for the third quarter and year-to-date as of September 30, 2019 as well as recent events (Press release, Geron, NOV 6, 2019, View Source [SID1234550466]). The Company ended the third quarter with $159.3 million in cash and marketable securities.

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"Geron has continued to execute on its 2019 development plans," said John A. Scarlett, M.D., Chairman and Chief Executive Officer. "In the third quarter, we completed the transition of the imetelstat program back to Geron, and we announced that the FDA granted Fast Track designation to imetelstat in relapsed/refractory myelofibrosis. In October, we announced the first patient dosed in the IMerge Phase 3 trial, and we are currently focused on patient recruitment and enrollment. Another priority is to prepare for an End of Phase 2 meeting with the FDA to discuss potential late-stage development of imetelstat in relapsed/refractory MF. All of these activities support the development of imetelstat as a potential treatment to address unmet medical needs in hematologic myeloid malignancies."

IMerge Phase 3 Clinical Trial – First Patient Dosed

In August 2019, Geron opened the IMerge Phase 3 clinical trial for screening and enrollment. On October 10, 2019, the Company announced that the first patient was dosed in the IMerge Phase 3 clinical trial.

IMerge is a two-part Phase 2/3 clinical trial of imetelstat in transfusion dependent patients with lower risk MDS who are relapsed/refractory to erythropoiesis-stimulating agents (ESAs). The primary endpoint is 8-week TI rate, which is defined as the proportion of patients achieving transfusion independence during any consecutive eight weeks since entry into the trial. Key secondary endpoints include the rate of transfusion independence lasting at least 24 weeks, or 24-week TI rate, durability of transfusion independence and the amount and relative change in transfusions.

The IMerge Phase 3 clinical trial is planned to enroll approximately 170 patients in a randomized, double-blind, placebo-controlled clinical trial to test the hypothesis that imetelstat improves the rate of red blood cell transfusion independence (TI). A target patient population of non-del(5q) lower risk MDS patients who are naïve to treatment with hypomethylating agents (HMAs) and lenalidomide was identified in Part 1 of IMerge, or the Phase 2 portion, and will be enrolled in the Phase 3. The trial is planned to be conducted at multiple medical centers globally, including North America, Europe, Middle East and Asia.

Phase 2 data from Part 1 of IMerge reported earlier this year suggested meaningful and durable transfusion independence, as well as potential disease-modifying activity and transfusion independence across different MDS patient subgroups, potentially achievable with imetelstat treatment. Many key aspects from Part 1 of IMerge remain the same for the Phase 3, including the primary and secondary endpoints, the dose and schedule of imetelstat administration, the target patient population, and a majority of the clinical sites that participated in the Phase 2.

Based upon current planning assumptions, Geron expects top-line results for the IMerge Phase 3 clinical trial to be available by mid-year 2022.

Completed Transition of Imetelstat Program Back to Geron

As of the end of September 2019, the transition of the imetelstat program back to Geron has been completed, including the transfer of the remaining non-clinical, manufacturing and ex-U.S. clinical and regulatory responsibilities from Janssen Biotech, Inc. (Janssen). Geron is now the sponsor of both the IMbark and IMerge clinical trials in all countries.

In June 2019, Geron entered into a Clinical Supply Agreement with Janssen to purchase certain inventories of drug product, drug substance and raw materials for imetelstat manufacturing. The delivery and testing of materials under the Clinical Supply Agreement is expected to be completed by the end of December 2019 with payment to Janssen to occur in the first quarter of 2020.

Fast Track Designation – Relapsed/Refractory Myelofibrosis (MF)

On September 30, 2019, Geron announced that the United States Food and Drug Administration (FDA) granted Fast Track designation to imetelstat for the treatment of adult patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus kinase (JAK) inhibitor treatment, or relapsed/refractory MF. The Fast Track designation includes patients with primary MF and MF developed after essential thrombocythemia or polycythemia vera. This is the same patient population that was studied in Geron’s IMbark Phase 2 clinical trial. There are currently no marketed drugs specifically approved for relapsed/refractory MF, representing a significant unmet medical need. Geron plans to conduct an End of Phase 2 meeting with the FDA by the end of the first quarter of 2020, and will subsequently provide a decision regarding potential late-stage development of imetelstat in relapsed/refractory MF.

The FDA’s Fast Track Program is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious conditions and supported by data that demonstrate the potential to address an unmet medical need. Fast Track designation provides opportunities for frequent interactions with FDA review staff, including meetings to discuss the drug’s development plan and to ensure the collection of appropriate data needed to support approval. Through the Fast Track Program, a product candidate may be eligible for priority review, if supported by the clinical data, and for the ability to submit completed sections of a New Drug Application (NDA) on a rolling basis as data become available prior to completion of the full application.

Third Quarter and Year-to-Date 2019 Results

For the third quarter of 2019, the Company reported a net loss of $15.2 million, or $0.08 per share, compared to $5.6 million, or $0.03 per share, for the third quarter of 2018. Net loss for the first nine months of 2019 was $39.5 million, or $0.21 per share, compared to $19.7 million, or $0.11 per share, for the first nine months of 2018.

Revenues for the three and nine months ended September 30, 2019 were $131,000 and $289,000, respectively, compared to $165,000 and $691,000 for the same periods in 2018. Revenues for the three and nine months ended September 30, 2019 and 2018 included royalty and license fee revenues under various non-imetelstat license agreements. The decline in revenues reflects a reduction in the number of active research license agreements in 2019 related to the Company’s human telomerase reverse transcriptase, or hTERT, technology as a result of patent expirations on the underlying technology.

Total operating expenses for the three and nine months ended September 30, 2019 were $16.1 million and $42.8 million, respectively, compared to $7.0 million and $22.2 million for the same periods in 2018. Research and development expenses for the three and nine months ended September 30, 2019 were $11.1 million and $27.1 million, respectively, compared to $2.7 million and $8.4 million for the same periods in 2018. The increase in research and development expenses, compared to the same periods in 2018, primarily reflects costs for the transition of the imetelstat program, including resuming sponsorship of the ongoing imetelstat clinical trials; expenses for start-up activities for the IMerge Phase 3 clinical trial; and higher personnel-related costs for the expanding development team. General and administrative expenses for the three and nine months ended September 30, 2019 were $5.0 million and $15.6 million, respectively, compared to $4.3 million and $13.8 million for the same periods in 2018. The increase in general and administrative expenses, compared to the same periods in 2018, primarily reflects higher corporate and patent legal costs and increased personnel-related expenses for additional headcount to support the development organization.

Interest and other income for the three and nine months ended September 30, 2019 was $1.0 million and $3.3 million, respectively, compared to $1.1 million and $2.2 million for the same periods in 2018. The overall increase in interest and other income, compared to 2018, primarily reflects higher yields on the Company’s increased marketable securities portfolio.

The Company ended the third quarter of 2019 with $159.3 million in cash and marketable securities. Since May 2019, the Company has raised cumulative net cash proceeds of approximately $19.3 million from the sales of an aggregate of 13,214,867 shares of common stock under an At Market Issuance Sales Agreement, after deducting sales commissions and other offering expenses payable by Geron. The Company expects these net cash proceeds to provide additional financial flexibility as it advances the imetelstat development program. The funds will support future development costs, including the IMerge Phase 3 clinical trial.

2019 Financial Guidance Reaffirmed

For fiscal year 2019, the Company expects total operating expenses to range from $80 to $85 million, of which approximately $20 to $25 million represents one-time costs that include imetelstat program transition activities from Janssen to Geron and purchase of drug product, drug substance and raw materials from Janssen to supply the IMerge Phase 3 trial and prepare for new drug manufacturing. In the third quarter of 2019, the Company completed the transition of the imetelstat program from Janssen.

As of October 31, 2019, the Company had 42 employees, and plans to grow to a total of approximately 45 to 50 employees by year-end 2019, of whom half will be research and development personnel.

Conference Call

Geron will host a conference call to discuss third quarter and year-to-date financial results as well as recent events at 8:00 a.m. ET on Thursday, November 7, 2019.

Participants may access the conference call live via telephone by dialing domestically +1 (866) 393-4306 or internationally +1 (734) 385-2616. The conference ID is 2929819. A live, listen-only webcast will also be available on the Company’s website at www.geron.com/investors/events. If you are unable to listen to the live call, an archived webcast will be available on the Company’s website for 30 days.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Early clinical data suggest imetelstat may have disease-modifying activity through the suppression of malignant progenitor cell clone proliferation, which allows potential recovery of normal hematopoiesis. Ongoing clinical studies of imetelstat consist of IMerge, a Phase 2/3 trial in lower risk myelodysplastic syndromes (MDS), and IMbark, a Phase 2 trial in Intermediate-2 or High-risk myelofibrosis (MF). Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis-stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus kinase (JAK) inhibitor treatment.

On November 6, 2019 Genmab reported that Interim Report for the First Nine Months Ended September 30, 2019 (Press release, Genmab, NOV 6, 2019, View Source [SID1234550465]).

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Highlights

Completion of public offering and listing of American Depository Shares (ADSs) on Nasdaq Global Select Market under the symbol "GMAB." Total gross proceeds from the issuance of new shares amounted to USD 582 million (DKK 3,873 million) with a corresponding increase in share capital of 3,277,500 ordinary shares or 32,775,000 ADSs
Positive data reported by Novartis for the Phase III ASCLEPIOS I & II studies of subcutaneous ofatumumab in relapsing multiple sclerosis (RMS)
DARZALEX (daratumumab) approved in the U.S. in combination with bortezomib, thalidomide and dexamethasone (VTd) and in Japan in combination with bortezomib, melphalan and prednisone (VMP) in various multiple myeloma frontline settings
Positive topline results for daratumumab in both the Phase III CANDOR and Phase II GRIFFIN studies in various multiple myeloma settings
Biologics License Application (BLA) submitted to U.S. Food and Drug Administration (U.S. FDA) for the subcutaneous formulation of daratumumab; standard review received. An extension of marketing authorization for this formulation was also submitted to the European Medicines Agency (EMA)
DARZALEX net sales increased 50% compared to the first nine months of 2018 to USD 2,168 million, resulting in royalty income of DKK 2,033 million

Genmab is improving its 2019 financial guidance mainly due to positive foreign exchange movements between the USD and DKK resulting in increased milestone income and royalties on sales of DARZALEX
"Genmab made excellent progress across many areas of the business during the third quarter of 2019. Of key significance was the completion of our public offering of American Depositary Shares and listing on the Nasdaq Global Select Market in the U.S. Genmab’s status as a dual listed company both increases our visibility as an innovation powerhouse and provides additional support for the development of our exciting pipeline of antibody product candidates," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "Over the past three months advances to this pipeline included positive data readouts for ofatumumab in relapsing multiple sclerosis and daratumumab in multiple myeloma, regulatory submissions for daratumumab and teprotumumab and additional approvals for daratumumab in the U.S. and Asia. In addition, we entered into new strategic collaborations with companies such as Tempus and BliNK Biomedical, which will allow us to expand our pipeline in new directions as Genmab continues to move towards our goal of transforming cancer treatment."

Financial Performance First Nine Months of 2019

Revenue was DKK 2,405 million in the first nine months of 2019 compared to DKK 1,789 million in the first nine months of 2018. The increase of DKK 616 million, or 34%, was mainly driven by higher DARZALEX royalties and reimbursement income from our collaborations with Seattle Genetics and BioNTech, partly offset by the one-time payment from Novartis of USD 50 million (DKK 304 million) during the first nine months of 2018 for lost potential milestones and royalties following announcement of Novartis’ intention to transition Arzerra (ofatumumab) to limited availability via compassionate use programs for chronic lymphocytic leukemia (CLL) in non-U.S. markets.
Net sales of DARZALEX by Janssen were USD 2,168 million in the first nine months of 2019 compared to USD 1,441 million in the first nine months of 2018, an increase of USD 727 million, or 50%.
Operating expenses were DKK 1,943 million in the first nine months of 2019 compared to DKK 1,130 million in the first nine months of 2018. The increase of DKK 813 million, or 72%, was driven by the advancement of tisotumab vedotin and enapotamab vedotin, additional investments in our product pipeline, and the increase in new employees to support the expansion of our product pipeline.
Operating income was DKK 462 million in the first nine months of 2019 compared to DKK 659 million in the first nine months of 2018. As anticipated, the decrease of DKK 197 million, or 30%, was driven primarily by increased operating expenses and the one-time payment from Novartis in 2018.
Outlook
Genmab is improving its 2019 financial guidance published on August 14, 2019 mainly due to positive foreign exchange movements between the USD and DKK resulting in increased milestone income and royalties on sales of DARZALEX.

MDKK Revised Guidance Previous
Guidance
Revenue 5,100 4,800
Operating expenses (2,750) (2,750)
Operating income 2,350 2,050
Conference Call
Genmab will hold a conference call in English to discuss the results for the first nine months of 2019 today, Wednesday, November 6, at 6:00 pm CET, 5:00 pm GMT or 12:00 pm EST. To join the call dial
+1 631 510 7495 (U.S. participants) or +44 2071 928000 (international participants) and provide conference code 7996106.

A live and archived webcast of the call and relevant slides will be available at www.genmab.com.

On November 6, 2019 Genmab A/S (Nasdaq: GMAB) reported that 37 abstracts related to Genmab owned and partnered programs were accepted for presentation at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place December 7-10 in Orlando, Florida (Press release, Genmab, NOV 6, 2019, View Source [SID1234550464]). Abstracts accepted for presentation include preliminary dose-escalation data from the ongoing Phase I trial of DuoBody-CD3xCD20 (GEN3013) in B-cell non-Hodgkin lymphomas, which will be presented during an oral session of the conference. Accepted abstracts also include pre-clinical data from Genmab’s next generation CD38 antibody, HexaBody-CD38, and updates on multiple daratumumab clinical trials.

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All abstracts are available on the ASH (Free ASH Whitepaper) website at www.hematology.org. Details regarding the key abstracts to be presented are included below.

"2019 has been a banner year for Genmab as we advance our proprietary pipeline into the clinic, and we look forward to ending the year on a high note with two key firsts; the first presentation of dose-escalation data from DuoBody-CD3xCD20 and the first presentation of pre-clinical data from HexaBody-CD38," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "We are also very pleased to see that, once again, a significant number of daratumumab abstracts were accepted for presentation at the prestigious ASH (Free ASH Whitepaper) conference, as this underscores our confidence in the wide potential of daratumumab."

Late breaking abstracts are not yet available.

On December 9 at 8:00 PM EST (2:00 AM CET / 1:00 AM GMT on 10 December) Genmab will hold its 2019 R&D Update and ASH (Free ASH Whitepaper) Data Review in Orlando, Florida. The event will be webcast live and details, including the webcast link, may be found on Genmab’s website in early December. This meeting is not an official program of the ASH (Free ASH Whitepaper) Annual Meeting.

Genmab Abstracts

First-in-Human, Phase 1/2 Trial to Assess the Safety and Clinical Activity of Subcutaneous GEN3013 (DuoBody-CD3×CD20) in B-cell Non-Hodgkin Lymphomas – Oral presentation, Monday, December 9

DuoBody-CD3xCD20 induces potent anti-tumor activity in malignant lymph node B cells from patients with DLBCL, FL and MCL ex vivo, irrespective of prior treatment with CD20 monoclonal antibodies – Poster presentation, Monday, December 9

Hexabody-CD38, a Novel CD38 Antibody with a Hexamerization Enhancing Mutation, Demonstrates Enhanced Complement-Dependent Cytotoxicity and Shows Potent Anti-Tumor Activity in Preclinical Models of Hematological Malignancies – Poster presentation, Sunday, December 8

Daratumumab Abstracts Sponsored by Janssen Biotech, Inc.

Oral Presentations:
Daratumumab Plus Bortezomib, Melphalan and Prednisone Versus Bortezomib, Melphalan and Prednisone in Patients with Transplant-ineligible Newly Diagnosed Multiple Myeloma: Overall Survival in ALCYONE– Oral presentation, Monday, December 9

Daratumumab Maintenance Therapy Improves Depth of Response and Results in Durable Progression-free Survival Following Daratumumab plus Cyclophosphamide, Bortezomib and Dexamethasone Induction Therapy in Multiple Myeloma: Update of the LYRA Study– Oral presentation, Monday, December 9

Depth of Response to Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone Improves Over Time in Patients with Transplant-eligible Newly Diagnosed Multiple Myeloma: GRIFFIN Study Update – Oral presentation, Monday, December 9

Evaluation of the Prognostic Value of Positron Emission Tomography-Computed Tomography at Diagnosis and Follow-up in Transplant-eligible Newly Diagnosed Multiple Myeloma Patients Treated in the Phase 3 CASSIOPEIA Study: Results of the CASSIOPET Companion Study – Oral presentation, Monday, December 9

Poster Presentations:
Randomized Phase 2 Study of Subcutaneous Daratumumab Plus Carfilzomib/Dexamethasone Versus Carfilzomib/Dexamethasone Alone in Patients with Multiple Myeloma who have been Previously Treated with Intravenous Daratumumab to Evaluate Retreatment (LYNX) – Poster presentation, Saturday, December 7

Daratumumab Plus Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma Ineligible for Transplant: Updated Analysis of MAIA – Poster presentation, Saturday, December 7

Final Analysis of a Phase 1b Study of Daratumumab in Combination with Carfilzomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma – Poster presentation, Saturday, December 7

Daratumumab Monotherapy for Patients with Relapsed or Refractory Natural Killer/T-cell Lymphoma, Nasal Type: Updated Results from an Open-label, Single-arm, Multicenter Phase 2 Study – Poster presentation, Saturday, December 7

Four-Year Follow-up of the Phase 3 POLLUX Study of Daratumumab Plus Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone Alone in Relapsed or Refractory Multiple Myeloma – Poster presentation, Saturday, December 7

Daratumumab Plus Lenalidomide Versus Lenalidomide Alone as Maintenance Treatment in Patients with Newly Diagnosed Multiple Myeloma after Frontline Autologous Stem Cell Transplant: Use of Minimal Residual Disease as a Novel Primary Endpoint in the Phase 3 AURIGA Study – Poster presentation, Saturday, December 7

Randomized, Open-Label, Non-inferiority, Phase 3 Study of Subcutaneous Versus Intravenous Daratumumab Administration in Patients with Relapsed or Refractory Multiple Myeloma: Body Weight Subgroup Analysis of COLUMBA – Poster presentation, Saturday, December 7

Randomized, Open-Label, Non-inferiority, Phase 3 Study of Subcutaneous Versus Intravenous Daratumumab Administration in Patients with Relapsed or Refractory Multiple Myeloma: COLUMBA Update – Poster presentation, Saturday, December 7

Daratumumab Subcutaneous Delivery in Relapsed or Refractory Multiple Myeloma: Population Pharmacokinetics and Exposure-response Analysis – Poster presentation, Sunday, December 8

Subcutaneous Daratumumab Plus Standard Treatment Regimens in Patients with Multiple Myeloma Across Lines of Therapy: PLEIADES Study Update – Poster presentation, Sunday, December 8

Efficacy and Safety of Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in First Relapse Patients with Multiple Myeloma: Four-Year Update of CASTOR – Poster presentation, Sunday, December 8

On November 6, 2019 FORMA Therapeutics, Inc., a clinical stage biopharmaceutical company focused on rare hematological diseases and cancers, reported that three abstracts have been accepted for presentation at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held in Orlando, Florida from December 7-10, 2019 (Press release, Forma Therapeutics, NOV 6, 2019, View Source [SID1234550463]).

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Three oral presentations on lead assets will feature data: olutasidenib, a next generation inhibitor of mutated isocitrate dehydrogenase 1 (IDH1m) in development for the treatment of patients with relapsed/refractory acute myeloid leukemia (RR/AML) or myelodysplastic syndrome (MDS), and patients with glioma and other solid tumors with an IDH1 mutation; and FT-4202, a novel selective red blood cell (RBC) pyruvate kinase (PKR) activator in development as a potentially disease-modifying therapy for the treatment of sickle cell disease (SCD). A poster presentation will feature data for a FORMA-discovered asset licensed to Celgene Corporation, FT-1101, an oral, structurally distinct and potent pan-inhibitor of the Bromodomain and Extra-Terminal (BET) epigenetic protein family.

The accepted abstracts are available online through the ASH (Free ASH Whitepaper) conference website, View Source, and include:

Oral Presentations

Title: Olutasidenib (FT-2102), an IDH1m Inhibitor As a Single Agent or in Combination with Azacitidine, Induces Deep Clinical Responses with Mutation Clearance in Patients with Acute Myeloid Leukemia Treated in a Phase 1 Dose Escalation and Expansion Study

Date/Time: Saturday, December 7, 2019 at 2:30 p.m. ET
Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Novel Targets and Combinations
Abstract: 231
Location: Orange County Convention Center, Chapin Theater (W320)
Presenter: Justin Watts, MD. Assistant Professor University of Miami, Sylvester Comprehensive Cancer Center

Title: Olutasidenib (FT-2102), Induces Rapid Remissions in Patients with IDH1-Mutant Myelodysplastic Syndrome: Results of Phase 1/2 Single Agent Treatment and Combination with Azacitidine

Date/Time: Monday, December 9, 2019 at 10:45 a.m. ET
Session: 637. Myelodysplastic Syndromes – Clinical Studies: Targeting Gene Mutations in MDS
Abstract: 674
Location: Orange County Convention Center, W311ABCD
Presenter: Jorge E. Cortes, MD. Professor, Augusta University, Director of the Georgia Cancer Center

Title: Phase 1 Single (SAD) and Multiple Ascending Dose (MAD) Studies of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of FT-4202, an Allosteric Activator of Pyruvate Kinase-R, in Healthy and Sickle Cell Disease Subjects

The presentation will report the effects of FT-4202 on healthy subjects in this ongoing study.

Date/Time: Monday, December 9, 2019 at 11:15 a.m. ET
Session: 114. Hemoglobinopathies, Excluding Thalassemia—Clinical: Emerging Therapies: Reports from Recent Clinical Trials
Abstract: 616
Location: Orange County Convention Center, W304ABCD
Presenter: Theodosia Kalfa, MD, PhD. Associate Professor, University of Cincinnati Department of Pediatrics, Cincinnati Children’s Hospital Medical Center

Poster Presentation

Title: Phase 1 Dose Escalation and Expansion Study to Determine Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the BET Inhibitor FT-1101 As a Single Agent in Patients with Relapsed or Refractory Hematologic Malignancies

Date/Time: Monday, December 9, 2019 from 6:00 – 8:00 p.m. ET
Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster III
Abstract: 3907
Location: Orange County Convention Center, Hall B
Presenter: Manish Patel, MD. Director of Drug Development, Florida Cancer Specialists. Associate Director of Drug Development, Sarah Cannon Research Institute

About Olutasidenib (FT-2102)

FORMA’s most advanced clinical asset, olutasidenib, is a potent and selective next generation inhibitor of mutated isocitrate dehydrogenase 1 (IDH1) being investigated to treat patients with relapsed/refractory acute myeloid leukemia (RR/AML) or myelodysplastic syndrome (MDS), and patients with glioma and other solid tumors with an IDH1 mutation. IDH1 is a natural enzyme that is part of the normal metabolism of all cells. Mutations of IDH1 can produce excessive amounts of the oncometabolite 2-hydroxyglutarate (2-HG), which impairs cell differentiation and promotes blood malignancies and solid tumors. IDH1 mutations are present in 7-14% of patients with AML and 3-4% of patients with MDS.

About FT-4202

FT-4202 is a novel selective red blood cell (RBC) pyruvate kinase (PKR) activator designed to be a disease-modifying therapy for the treatment of sickle cell disease (SCD), with a multimodal approach. FT-4202 works upstream by activating the RBCs’ natural PKR activity to decrease 2,3-DPG levels, which leads hemoglobin to hold on to oxygen molecules longer to reduce RBC sickling. The downstream activity of FT-4202 increases ATP levels, the fuel that provides energy to cells, to improve RBC health and survival. Together, these effects are anticipated to increase hemoglobin levels and decrease painful vaso-occlusive crises. SCD is the most common disorder caused by a single gene mutation and affects approximately 100,000 people in the U.S., and millions globally.

About FT-1101 (also known as CC-95775)

FT-1101 (also known as CC-95775) is an oral, structurally distinct and potent pan-inhibitor of the Bromodomain and Extra-Terminal (BET) epigenetic protein family, which was discovered by FORMA and licensed to Celgene Corporation.

On November 6, 2019 Five Prime Therapeutics, Inc. (NASDAQ: FPRX), a clinical-stage biotechnology company focused on developing immune modulators and precision therapies for solid tumor cancers, reported its results for the third quarter and provided an update on the company’s recent activities (Press release, Five Prime Therapeutics, NOV 6, 2019, View Source [SID1234550462]).

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"We have advanced all of our wholly-owned programs according to our plan for 2019," said Willilam Ringo, Chairman and interim Chief Executive Officer of Five Prime Therapeutics. "As we approach 2020, we have repositioned Five Prime with a focus on prioritizing our pipeline based on upcoming data readouts, while also extending our cash runway, in order to maximize the long-term potential of the company."

Third Quarter 2019 Business Highlights and Milestones

Clinical Pipeline:

Bemarituzumab (anti-FGFR2b) is a first-in-class isoform-selective antibody with enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) in development as a targeted immunotherapy for tumors that overexpress FGFR2b. Bemarituzumab is being evaluated in combination with mFOLFOX6 in the Phase 3 FIGHT (FGFR2b Inhibition in Gastric and Gastroesophageal Junction Cancer Treatment) trial.

The company has enrolled approximately 140 patients with newly diagnosed advanced stage gastric cancer into the FIGHT trial, representing approximately 25% of projected total trial enrollment, and has paused pre-screening of patients for enrollment in the trial.

The prevalence of FGFR2b overexpression in this patient population is approximately 30% based on global pre-screening data.

The company expects to conduct a planned futility analysis for the FIGHT trial in mid-2020. The purpose of the futility analysis is to ensure the trial is adequately powered to detect an overall survival benefit at full enrollment.

FPA150 (anti-B7-H4) is a first-in-class B7-H4 antibody designed to target tumor cells by enhancing killing of B7-H4 overexpressing tumors through ADCC and by blocking B7-H4 from sending an inhibitory signal to CD8 T cells. B7-H4 is frequently overexpressed in breast, ovarian and endometrial cancers.

The company presented a poster at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress with preliminary FPA150 efficacy results from the monotherapy Phase 1b expansion cohorts at the 20mg/kg dose in patients with breast, ovarian or endometrial cancers that overexpress B7-H4.

As of the August 9, 2019 data cut-off date, one patient in the ovarian cohort had a confirmed response; 11 patients had stable disease and remained on therapy. As of the data cut-off date, 31 patients across the ovarian, endometrial and breast cohorts were evaluable for response.

The company also presented safety data for four patients in the combination arm of FPA150 with Keytruda (pembrolizumab) suggesting that FPA150 could be combined at a full dose of 20 mg/kg every three weeks with the standard dose of pembrolizumab.

FPT155 (CD80-Fc) is a first-in-class CD80-Fc fusion protein that uses the binding interactions of soluble CD80 to directly engage CD28 to enhance its co-stimulatory T cell activity without inducing super agonism and to block CTLA-4 from competing for endogenous CD80, allowing CD28 signaling to prevail in T cell activation in the tumor microenvironment.

On November 9, the company will present initial safety data from the Phase 1 clinical trial of FPT155 in patients with advanced solid tumors in a poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting in National Harbor, Maryland.

FPT155 data presented at SITC (Free SITC Whitepaper) will include initial safety results from the Phase 1a dose escalation portion of the trial, which is designed to characterize the safety and pharmacokinetic (PK)/pharmacodynamic (PD) profile of FPT155 and identify a recommended dose for the Phase 1b portion of the trial.

Cabiralizumab (anti-CSF1R) is an antibody that inhibits CSF1R and has been shown to block the activation and survival of tumor-associated macrophages. Pursuant to a worldwide collaboration agreement, Bristol-Myers Squibb (BMS) has an exclusive worldwide license for the development and commercialization of cabiralizumab, and Five Prime retains the rights to a U.S. co-promotion option.

Bristol-Myers Squibb has completed enrollment in the randomized Phase 2 trial testing the combination of cabiralizumab with Opdivo (nivolumab) with and without chemotherapy in approximately 160 patients with locally advanced or metastatic pancreatic cancer that has progressed during or after one line of chemotherapy.

The next anticipated event from the Phase 2 trial is the announcement of actionable data from BMS in 2020.

BMS-986258 (anti-TIM-3) is a fully-human monoclonal antibody targeting TIM-3 (T cell immunoglobulin and mucin domain-3), an immune checkpoint receptor that may limit the duration and magnitude of T cell responses. This is the first clinical candidate from the discovery collaboration between Five Prime and BMS that includes targets in three immune checkpoint pathways.

The Phase 1/2 clinical trial continues to progress, with the expected size of the trial increased to 383 patients in July 2019.

Corporate Highlights

In October, the company announced a corporate restructuring to extend its cash runway without impacting or delaying the data timelines of its clinical programs. The company will retain a small research group focused on advancing three wholly-owned, late-stage research programs.

In September, the company’s board of directors appointed William Ringo as interim Chief Executive Officer in addition to his position as Chairman of the Board of Directors.

Summary of Financial Results and Guidance:

Cash Position: Cash, cash equivalents and marketable securities totaled $186.0 million as of September 30, 2019, compared to $214.1 million as of June 30, 2019. The decrease in cash, cash equivalents and marketable securities was primarily attributable to quarterly operating expenses that exceeded quarterly revenues.

Revenue: Collaboration and license revenue for the third quarter of 2019 decreased by $2.8 million, or 48.3%, to $3.0 million from $5.8 million for the third quarter of 2018. This decrease was primarily related to the completion of the research term under the immuno-oncology research collaboration with BMS in March 2019 and from progress made towards the company’s performance obligation under the original collaboration agreement.

R&D Expenses: Research and development expenses for the third quarter of 2019 decreased by $17.8 million, or 39.8%, to $26.9 million from $44.7 million for the third quarter of 2018. This decrease was primarily due a one-time milestone payment triggered by the dosing of the first patient in the Phase 3 FIGHT trial in the third quarter of 2018. Lower compensation costs, pre-clinical and research activities, manufacturing and diagnostic expenses and the reduction in the use of temporary resources contributed to the decrease and were partially offset by increased clinical trial expense to advance the company’s bemarituzumab, FPA150, and FPT155 clinical programs.

G&A Expenses: General and administrative expenses for the third quarter of 2019 increased by $3.4 million, or 34.7%, to $13.2 million from $9.8 million for the third quarter of 2018. The increase was primarily due to increased compensation costs offset by a reduction in the use of temporary resources.

Net Loss: Net loss for the third quarter of 2019 was $36.1 million, or $1.03 per basic and diluted share, compared to a net loss of $47.2 million, or $1.37 per basic and diluted share, for the third quarter of 2018.

Shares Outstanding: Weighted average shares outstanding for the third quarter of 2019 was 34,996,298 as of September 30, 2019.

Cash Guidance: Five Prime expects full-year 2019 net cash used in operating activities to be between $117 and $122 million and estimates ending 2019 with cash, cash equivalents and marketable securities between $148 and $153 million.

Conference Call Information

Five Prime will host a conference call and live audio webcast today at 4:30 p.m. (ET) / 1:30 p.m. (PT) to discuss its financial results and provide a corporate update. To participate in the conference call, please dial (877) 878-2269 (domestic) or (253) 237-1188 (international) and refer to conference ID 5769473. To access the live webcast please visit the "Events & Presentations" page under the "Investors" tab on Five Prime’s website at www.fiveprime.com. An archived copy of the webcast will be available on Five Prime’s website beginning approximately two hours after the conference call. Five Prime will maintain an archived replay of the webcast on its website for at least 30 days after the conference call.