On August 7, 2019 Rexahn Pharmaceuticals, Inc. (NasdaqCM: REXN), a clinical stage biopharmaceutical company developing innovative therapies to improve patient outcomes in cancers that are difficult to treat, reported financial results for the three and six months ended June 30, 2019 and provided an update on RX-3117 development (Press release, Rexahn, AUG 7, 2019, View Source [SID1234538306]).

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!

Recent Highlights and RX-3117 Development Updates:

Announced a collaboration and license agreement with BioSense Global LLC, a New Jersey- and Suzhou, China-based biopharmaceutical company, to advance the development and commercialization of RX-3117 for pancreatic and other cancers in Greater China. Under the agreement, Rexahn will receive an upfront payment, a portion of which has been paid, and will be eligible to receive up to $126 million in development and regulatory milestones and up to $100 million in commercial milestones for each product containing RX-3117, contingent on achieving commercial goals.

As of July 24, 2019, an overall response rate of 23% has been observed in 40 patients that have had at least one scan on treatment in the Phase 2a study of RX-3117 in combination with ABRAXANE (paclitaxel protein-bound particles for injectable suspension) in patients newly diagnosed with metastatic pancreatic cancer. The Company previously reported in January 2019 an overall response rate of 38% in the first 24 patients who had at least one scan on treatment. Preliminary and unaudited data indicates that the median progression free survival for patients in the study is approximately 5.4 months. Patients currently active in the study will continue to be treated and final data from the trial is expected to be available in 2020.

Transferred its stock exchange listing to the Nasdaq Capital Market from its previous listing on NYSE American.

Effected a 1-for-12 reverse stock split of outstanding shares on April 12, 2019.

As of August 7, 2019, had approximately $15.3 million in cash, cash equivalents, and marketable securities (unaudited). Rexahn expects that its cash, cash equivalents and marketable securities will be sufficient to fund the company’s currently expected cash flow requirements for its activities for at least the next 12 months.

"We are surprised and disappointed with the most recent preliminary data from the ongoing Phase 2a trial of RX-3117 in combination with ABRAXANE in first line metastatic pancreatic cancer patients," said Douglas J. Swirsky president and chief executive officer of Rexahn. "RX-3117 appears to be well tolerated and we are evaluating development options for RX-3117 in other indications, including through our collaboration with BioSense. In the near term, we are focused on supporting our collaborations with BioSense and Zhejiang Haichang Biotechnology Co., Ltd. as we evaluate the best path forward for our programs."

See the discussion below under Important Cautionary Statements regarding our cash balance and the other forward-looking statements in this release.

Q2 2019 Financial Results:

R&D Expenses: Research and development expenses were $1.6 million for the three months ended June 30, 2019, compared to $3.4 million for the three months ended June 30, 2018. Research and development expenses were $3.9 million for the six months ended June 30, 2019, compared to $7.5 million for the six months ended June 30, 2018. The decrease in research and development expenses is primarily attributable to decreases in drug manufacturing and clinical trial costs and a reduction in preclinical programs and headcount.

G&A Expenses: General and administrative expenses were $1.3 million for the three months ended June 30, 2019 compared to $1.6 million for the three months ended June 30, 2018. General and administrative expenses were $3.0 million for the six months ended June 30, 2019 compared to $3.4 million for the six months ended June 30, 2018. The decrease is primarily attributable to a decrease in personnel expenses, offset by increases in professional fees.

Net Loss: Rexahn’s loss from operations was $3.0 million and $5.0 million for the three months ended June 30, 2019 and 2018, respectively. Rexahn’s net loss was $2.5 million, or $0.61 per share, for the three months ended June 30, 2019, compared to a net loss of $3.8 million, or $1.45 per share, for the three months ended June 30, 2018. For the six-month period ended June 30, 2019, Rexahn’s net loss was $4.8 million, or $1.23 per share, compared to a net loss of $5.9 million, or $2.24 per share for the six months ended June 30, 2018. The net loss for the six months ended June 30, 2019 and 2018 includes unrealized gains on the fair value of warrants of $1.9 million and $4.5 million, respectively. The fair value adjustments are non-cash charges and are primarily a result of changes in stock price between reporting periods.

On August 7, 2019 Moderna, Inc. (Nasdaq: MRNA), a clinical stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, reported financial results for the second quarter of 2019 and provided business updates (Press release, Moderna Therapeutics, AUG 7, 2019, View Source [SID1234538322]).

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!

New updates announced today include:

Infectious Diseases

Enrollment complete for Phase 1 CMV vaccine (mRNA-1647) study
Second planned interim analysis of Phase 1 hMPV and PIV3 vaccine (mRNA-1653) study showed antibody titers remained above baseline at all dose levels at seven months
First subject dosed in Phase 1 RSV vaccine (mRNA-1172 or Merck V172) study
First subject dosed in Phase 1 Zika vaccine (mRNA-1893) study
Immuno-Oncology

First patient consented in Phase 2 PCV (mRNA-4157) study in patients with resected melanoma
First patient dosed in Phase 1 KRAS cancer vaccine (mRNA-5671 or Merck V941) study
First patient dosed in Phase 1 study of mRNA encoding IL12 (MEDI1191) injected intratumorally
Rare Diseases

Six of eight subjects dosed in the third cohort (0.6 mg/kg) of the Phase 1 antibody against chikungunya virus (mRNA-1944) study; the lipid nanoparticle (LNP) formulation used for mRNA-1944 is also utilized in Moderna’s MMA program
Three clinical sites actively recruiting for Phase 1/2 MMA (mRNA-3704) study
Research

Vertex Pharmaceuticals extended the companies’ research collaboration in cystic fibrosis (CF)
"Since our last quarterly update, our personalized cancer vaccine program with Merck has advanced into Phase 2, the cytomegalovirus vaccine Phase 1 study has completed enrollment and four new Phase 1 trials in immuno-oncology and infectious diseases have begun," said Stéphane Bancel, Moderna’s chief executive officer. "We are pleased by the advancement of our programs and look forward to sharing new clinical data in the near term. Additionally, we are excited that Vertex extended our research collaboration based on the teams’ progress to date. Our balance sheet remains strong, and we continue to deploy our capital toward the advancement and expansion of our development pipeline and the creation of potential new modalities."

Moderna currently has 21 mRNA development candidates in its portfolio with 13 in clinical studies. Across Moderna’s pipeline, more than 1,000 subjects have been enrolled in clinical studies. The Company’s updated pipeline can be found at View Source Moderna and collaborators have published more than 35 peer-reviewed papers, including 23 over the last 12 months.

Summary of Recent Highlights by Modality

Prophylactic vaccines: Moderna is developing vaccines against viral diseases where there is unmet medical need – including complex vaccines with multiple antigens for common diseases, as well as vaccines against epidemic and pandemic threats to global public health.

Respiratory syncytial virus (RSV) vaccine (mRNA-1172 or V172): The first subject has been dosed in the Phase 1 study of mRNA-1172 led by Merck. mRNA-1172 has shown enhanced potency in preclinical studies compared with the companies’ first RSV candidate (mRNA-1777).
Cytomegalovirus (CMV) vaccine (mRNA-1647): The Phase 1 study of mRNA-1647 has been fully enrolled, at a top dose of 300µg. This randomized, observer-blind and placebo-controlled study is designed to evaluate the safety and immunogenicity of mRNA-1647, a vaccine encoding the gB and pentamer complexes of CMV. CMV is a common human pathogen and a leading cause of birth defects.
Human metapneumovirus (hMPV) and parainfluenza type 3 (PIV3) vaccine (mRNA-1653): Topline data from a second planned interim analysis of an ongoing Phase 1 randomized, observer-blind, placebo-controlled and dose-ranging study in healthy adults showed that hMPV and PIV3 serum neutralizing antibody titers remained above baseline through seven months and the vaccine was generally well-tolerated. Topline data from the study’s first interim analysis, announced in February 2019, showed that mRNA-1653 boosted antibody titers one month after vaccination at all dose levels and was generally well-tolerated. Data from the study will be presented at IDWeek on October 2 – 6, 2019 in Washington, D.C. In a recent type C meeting with the U.S. Food and Drug Administration (FDA), the Company discussed a potential path forward to evaluate protection against both hMPV and PIV3 in a single Phase 3 study. Consistent with this development path, Moderna is planning to initiate a Phase 1b study of mRNA-1653 in seropositive toddler subjects as the next step.
Zika virus vaccine (mRNA-1893): The first subject has been dosed in the Phase 1 study of mRNA-1893. This development candidate is being developed in collaboration with the U.S. Biomedical Advanced Research and Development Authority (BARDA) within the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services.
Publications of note: In May, Moderna published its clinical data in Vaccine from two Phase 1 studies showing that mRNA vaccines against H10N8 and H7N9 influenza viruses were well-tolerated and elicited robust immune responses. In July, Moderna published preclinical data in the Journal of Infectious Diseases demonstrating the ability of mRNA vaccines to protect against congenital Zika virus infection in mice.
Cancer Vaccines: These programs focus on stimulating a patient’s immune system with antigens derived from tumor-specific mutations to enable the immune system to elicit a more effective anti-tumor response.

Personalized cancer vaccines (PCVs) (mRNA-4157, NCI-4650): The first patient has been consented for the randomized Phase 2 study investigating Merck’s pembrolizumab (KEYTRUDA) in combination with a 1 mg dose of mRNA-4157, compared to pembrolizumab alone, for the adjuvant treatment of high-risk resectable melanoma. Additionally, the protocol for the ongoing Phase 1 trial has been amended to include a cohort of 17 patients who are refractory to PD-1 inhibitors.
KRAS vaccine (mRNA-5671 or V941): The first patient was dosed in the Phase 1 open-label, multi-center study to evaluate the safety and tolerability of mRNA-5671 both as a monotherapy and in combination with pembrolizumab. The study, led by Merck, will enroll patients with KRAS mutant advanced or metastatic non-small cell lung cancer, colorectal cancer or pancreatic adenocarcinoma, and centrally confirmed Human Leukocyte Antigen (HLA) HLA-A*1101 and/or HLA-C*0802 allele expression. mRNA-5671 is designed to generate and present the four most prevalent KRAS mutations as neoantigens to the immune system. These four mutations comprise an estimated 80-90 percent of KRAS mutations in the study indications.
Presentations of note: Moderna presented interim data from its ongoing Phase 1 study of PCV candidate mRNA-4157, demonstrating safety, tolerability and immunogenicity of mRNA-4157 alone and in combination with pembrolizumab, at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Additionally, the National Cancer Institute (NCI) also presented data at ASCO (Free ASCO Whitepaper) from its Phase 1 study of PCV mRNA-4650 as a monotherapy for patients with advanced metastatic cancers. The NCI program uses Moderna’s mRNA technology but uses a different neoantigen selection process and study design than Moderna’s Phase 1 mRNA-4157 study.
Intratumoral Immuno-Oncology: These programs aim to drive anti-cancer T cell responses by injecting mRNA therapies directly into tumors.

OX40L (mRNA-2416): Dosing is ongoing at the highest levels (8 mg) in the Phase 1/2 open-label, multi-center, dose escalation and efficacy study of intratumoral injections of mRNA-2416 in patients with advanced malignancies. A Phase 2 expansion cohort in patients with advanced ovarian carcinoma is preparing to start enrollment; this will include the combination of intratumoral mRNA-2416 with durvalumab (IMFINZI).
OX40L + IL23 + IL36γ (Triplet) (mRNA-2752): The first patient was dosed in the combination arm of the Phase 1 trial of mRNA-2752. This study is evaluating mRNA-2752 as a single agent and in combination with durvalumab in patients with accessible solid tumors and lymphomas. mRNA-2752 is an investigational mRNA immuno-oncology therapy that encodes a novel combination of three immunomodulators.
IL12 (MEDI1191): The first patient was dosed with MEDI1191 monotherapy in the Phase 1 open-label, multi-center study of intratumoral injections of MEDI1191 alone and in combination with a checkpoint inhibitor in patients with advanced solid tumors, being led by AstraZeneca. MEDI1191 is an mRNA encoding for IL12, a potent immunomodulatory cytokine.
Systemic Secreted Therapeutics: In this modality, mRNA is delivered systemically to create proteins that are secreted outside the cell with the aim of producing pharmaceutically active proteins with therapeutic effects across the human body.

Antibody against the chikungunya virus (mRNA-1944): Six of eight subjects have been dosed in the third cohort (0.6 mg/kg) of the Phase 1 antibody against chikungunya virus (mRNA-1944) study. This study is evaluating the safety and tolerability of escalating doses of mRNA-1944 via intravenous infusion in healthy adults. mRNA-1944 is the first monoclonal antibody encoded by mRNA to be dosed in a human and the first development candidate from Moderna’s systemic secreted therapeutics modality to start clinical testing. The lipid nanoparticle (LNP) formulation used for mRNA-1944 is also utilized in Moderna’s MMA program.
Publication of note: In May, Moderna published preclinical data in Science Immunology showing mRNA encoding an antibody against the chikungunya virus (mRNA-1944) was well-tolerated, resulted in linear dose-dependent protein expression and provided complete protection in preclinical species.
Systemic Intracellular Therapeutics: These programs aim to deliver mRNA into cells within target organs as a therapeutic approach for diseases caused by a missing or defective protein.

Methylmalonic acidemia (MMA) (mRNA-3704): Three clinical trial sites are open and actively recruiting patients for the Phase 1/2 open-label, dose escalation study evaluating mRNA-3704 for the treatment of MMA. The objectives of the study are to evaluate safety and tolerability, assess the pharmacodynamic response and characterize the pharmacokinetic profile of mRNA-3704. Moderna recently updated the study protocol to widen the age bracket of the first cohort for this trial to allow for the enrollment of pediatric patients (now includes patients 8 years and older, a modification from adolescents aged 12-18.) This is Moderna’s first rare disease program to advance into clinical testing.
MMA and propionic acidemia (PA) Natural History Study (MaP): As of July 15, 2019, a total of 71 patients have been enrolled in the study (35 MMA, 36 PA). This is a global, multi-center, non-interventional study for patients with confirmed diagnosis of MMA due to methylmalonyl-CoA mutase (MUT) deficiency or PA and is designed to identify and correlate clinical and biomarker endpoints for these disorders.
Publication of note: In July, Moderna published preclinical data in EBioMedicine, a Lancet publication, showing mRNA therapy demonstrated long-term efficacy and safety, with dose-dependent and reproducible biomarker responses, in mouse models of MMA.
Information about each development candidate in Moderna’s pipeline, including those discussed in this press release, can be found on the investor relations page of its website: View Source

Research Update

Vertex CF research collaboration: In July 2016, Moderna and Vertex announced an exclusive research collaboration and licensing agreement aimed at the discovery and development of mRNA therapeutics for the treatment of CF. Based on preclinical work to date, Vertex has extended this collaboration through the first quarter of 2020 with options to extend further based on future progress. Pulmonary mRNA delivery represents a potential new route of administration for Moderna.
Annual R&D Day

Moderna will host its annual R&D Day in New York City on September 12, 2019.
Investor Call and Webcast Information

Moderna will host a live conference call and webcast at 8:00 a.m. ET on Wednesday, August 7, 2019. To access the live conference call, please dial 866-922-5184 (domestic) or 409-937-8950 (international), and refer to conference ID 4799277. A webcast of the call will also be available under "Events and Presentations" in the Investors section of the Moderna website at View Source The archived webcast will be available on Moderna’s website approximately two hours after the conference call and will be available for 30 days following the call.

Second Quarter 2019 Financial Results

Cash Position: Cash, cash equivalents and investments as of June 30, 2019 and December 31, 2018 were $1.44 billion and $1.69 billion, respectively.
Net Cash Used in Operating Activities: Net cash used in operating activities was $256.1 million for the six months ended June 30, 2019 compared to $159.6 million for the six months ended June 30, 2018. Net cash used in operating activities includes $22.0 million and $25.0 million for the six months ended June 30, 2019 and 2018, respectively, of in-licensing payments to Cellscript, LLC and its affiliate, mRNA RiboTherapeutics, Inc., to sublicense certain patent rights. After the first quarter of 2019, we have no further in-licensing payment obligations to Cellscript and its affiliate.
Cash Used for Purchases of Property and Equipment: Cash used for purchases of property and equipment was $18.2 million for the six months ended June 30, 2019 compared to $66.0 million for the six months ended June 30, 2018.
Revenue: Total revenue was $13.1 million for the three months ended June 30, 2019 compared to $28.9 million for the three months ended June 30, 2018. Total revenue was $29.1 million for the six months ended June 30, 2019 compared to $57.9 million for the six months ended June 30, 2018. On January 1, 2019, we adopted Accounting Standards Codification (ASC) Topic 606, Revenue from Contracts with Customers (ASC 606), using the modified retrospective transition method applied to those contracts which were not completed as of January 1, 2019. The total revenue decreases in 2019 were due to decreases in collaboration revenue across all our strategic alliances, particularly AstraZeneca and Merck, largely driven by our adoption of ASC 606. Total revenue under the previous revenue recognition standard would have been $16.9 million and $55.5 million for the three months and six months ended June 30, 2019, respectively.
Research and Development Expenses: Research and development expenses were $128.5 million for the three months ended June 30, 2019 compared to $104.5 million for the three months ended June 30, 2018. The increase was primarily attributable to an increase in personnel related costs including stock-based compensation, an increase in lab supplies and materials, and an increase in clinical trial and manufacturing costs. Research and development expenses were $259.1 million for the six months ended June 30, 2019 compared to $194.6 million for the six months ended June 30, 2018. The increase was primarily attributable to an increase in personnel related costs including stock-based compensation, an increase in clinical trial and manufacturing costs, an increase in lab supplies and materials, and an increase in consulting and outside services.
General and Administrative Expenses: General and administrative expenses were $28.5 million for the three months ended June 30, 2019 compared to $21.4 million for the three months ended June 30, 2018. The increase was mainly due to an increase in personnel related costs including stock-based compensation, and an increase in consulting and outside services. General and administrative expenses were $55.8 million for the six months ended June 30, 2019 compared to $37.7 million for the six months ended June 30, 2018. These increases were mainly due to the additional costs of operating as a publicly traded company, including an increase in personnel related costs and stock-based compensation, an increase in consulting and outside services, and an increase in information technology, facility and insurance related costs.
Net Loss: Net loss was $135.1 million for the three months ended June 30, 2019 compared to $90.6 million for the three months ended June 30, 2018. Net loss was $267.7 million for the six months ended June 30, 2019 compared to $163.0 million for the six months ended June 30, 2018.
2019 Expected Cash Position

Moderna reiterated its expectation for cash, cash equivalents and investments at December 31, 2019 to be in the range of $1.15 billion to $1.20 billion.

On August 7, 2019 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that, subject to market and other conditions, it intends to offer $225 million aggregate principal amount of its convertible senior notes due 2024 (the "notes") in a private placement to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Press release, Clovis Oncology, AUG 7, 2019, View Source [SID1234538340]). Clovis Oncology also expects to grant the initial purchasers a 13-day option to purchase up to $33.75 million aggregate principal amount of additional notes on the same terms and conditions.

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 interest rate, conversion rate and other terms will be determined at the time of pricing of the offering of the notes. The holders of the notes may convert their notes at their option at any time prior to the close of business on the business day immediately preceding the maturity date. Clovis Oncology will not have the right to redeem the notes prior to their maturity. Holders of the notes may require Clovis Oncology to repurchase for cash all or part of their notes upon certain fundamental changes at a repurchase price equal to 100% of the principal amount of the notes to be repurchased, plus accrued and unpaid interest to, but excluding, the fundamental change repurchase date. In addition, following certain corporate events that occur prior to the maturity date, Clovis Oncology will, in certain circumstances, increase the conversion rate for a holder who elects to convert its notes in connection with such corporate event.

Concurrently with the offering, in separate transactions, Clovis Oncology intends to use a portion of the net proceeds from the offering to repurchase in privately negotiated transactions with a limited number of holders, a portion of Clovis Oncology’s outstanding 2.50% Convertible Senior Notes due 2021 (the "2021 Notes"), depending on negotiations and pricing determinations in connection with such proposed repurchase transactions. Any repurchase of the 2021 Notes could affect the market price of Clovis Oncology’s common stock. Clovis Oncology intends to use the remaining net proceeds from this offering for general corporate purposes, including sales and marketing expenses associated with Rubraca (rucaparib), funding of our development programs, payment of milestones pursuant to our license agreements, general and administrative expenses, acquisition or licensing of additional product candidates or businesses, repurchase or repayment of other debt obligations and working capital.

The offer and sale of the notes and the shares of common stock issuable upon conversion of the notes have not been registered under the Securities Act or any state securities laws and, unless so registered, the notes and any such shares may not be offered or sold in the United States except pursuant to an applicable exemption from the registration requirements of the Securities Act and applicable state securities laws. This press release does not constitute an offer to sell or the solicitation of an offer to buy the notes or any other securities, nor will there be any sale of notes or any other securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On August 7, 2019 Sangamo Therapeutics, Inc. (NASDAQ: SGMO), a genomic medicine company, reported second quarter 2019 financial results and recent business highlights (Press release, Sangamo Therapeutics, AUG 7, 2019, View Source [SID1234538369]).

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!

"We continue to progress our strategy to develop our diversified portfolio of genomic medicine product candidates using our expertise in gene therapy, cell therapy, genome editing and gene regulation," said Sandy Macrae, CEO of Sangamo. "Last month, we reported updated results for SB-525, our investigational gene therapy for hemophilia A. We are pleased with the emerging clinical profile and competitive positioning of SB-525 and are preparing for a Phase 3 registrational study with our partner Pfizer. The THALES study evaluating ST-400, a gene-edited cell therapy for beta thalassemia being developed with Sanofi, is progressing well and recently enrolled a fourth patient. In the upcoming months, two of our wholly owned programs, ST-920, an investigational gene therapy for Fabry disease, and TX-200, our first CAR-Treg product candidate, are also expected to advance into the clinic."

"We have observed significant increases in efficacy above a defined vector dose threshold with AAV6, the vector we use in our hemophilia gene therapy and our in vivo genome editing clinical programs," Dr. Macrae continued. "These recent insights into the kinetics of AAV6 suggest rational methods for improving the delivery of zinc finger nucleases, which we believe may substantially enhance the efficacy of in vivo genome editing, especially when added to the significantly increased potency that we expect to obtain with our updated gene editing reagents. We believe we can integrate these improvements rapidly and plan to introduce them as the next step forward for our in vivo genome editing clinical development programs. Based on current assumptions, including the timelines for manufacturing, we now expect that our next in vivo genome editing clinical trial will commence by year end 2020."

Recent Highlights

Clinical

In partnership with Pfizer, presented updated Phase 1/2 data for SB-525, an investigational gene therapy for the treatment of adults with hemophilia A. The data showed that SB-525 was generally well-tolerated and demonstrated a dose-dependent increase in Factor VIII (FVIII) activity levels. The first two patients treated at the 3e13 vg/kg dose rapidly achieved normal levels of FVIII activity, with no reported bleeding events or exogenous FVIII usage. The response was durable for at least 24 weeks, the extent of follow-up at the time of the data cut-off. The two patients most recently treated at the 3e13 vg/kg dose level are demonstrating FVIII activity kinetics that appear consistent with the first two patients treated in this dose cohort at similar early time points.

In July, dosed the fifth patient in the 3e13 vg/kg cohort (Patient 11 in the study), completing enrollment of the Phase 1/2 study evaluating SB-525

United States Food and Drug Administration granted regenerative medicine advanced therapy (RMAT) designation for SB-525 gene therapy to treat severe hemophilia A

Preparations have begun to advance SB-525 into a Phase 3 registrational clinical trial, including engagement with regulators and initiating the transfer of the SB-525 manufacturing process to Pfizer

Enrolled a fourth patient into the Phase 1/2 clinical trial for ST-400, an ex vivo gene-edited cell therapy candidate for the treatment of beta thalassemia, which is being developed in partnership with Sanofi. Sanofi is conducting a Phase 1/2 clinical trial evaluating BIVV003, a separate but related gene-edited cell therapy candidate for sickle cell disease.

Activated the first clinical site for the STAAR study evaluating ST-920, an investigational gene therapy candidate for Fabry disease. Sangamo expects to enroll the first patient by year end 2019.

Remain on track to file CTA in 2019 for TX200, a CAR-Treg product candidate, in HLA-A2 mismatched kidney transplantation

Kite, a Gilead Company, is planning to initiate a clinical study of KITE-037, an allogeneic anti-CD19 CAR-T, in 2020.

Research

Published a manuscript detailing the activity of disease allele-selective zinc finger proteins in preclinical models of Huntington’s disease in the July 2019 issue of Nature Medicine

Published a manuscript detailing two new approaches for optimizing the specificity of genome editing with zinc finger nucleases in the August 2019 issue of Nature Biotechnology

Corporate

Hired Gary Loeb as Executive Vice President and General Counsel

Second Quarter 2019 Financial Results

For the second quarter ended June 30, 2019, Sangamo reported a consolidated net loss of $30.3 million, or $0.26 per share, compared to a net loss of $16.6 million, or $0.17 per share, for the same period in 2018. As of June 30, 2019, the Company had cash, cash equivalents, and investments of $450.3 million.

Revenues for the second quarter ended June 30, 2019 were $17.5 million, compared to $21.4 million for the same period in 2018. The decrease was primarily due to a decline of $3.7 million in revenues related to the agreement with Pfizer due to a change in estimate resulting from the expansion of the project scope of the hemophilia A collaboration.

As anticipated, operating expenses increased in the second quarter ended June 30, 2019, reflecting the Company’s growth through the acquisition of TxCell, increased U.S. headcount in support of growth of the preclinical pipeline and clinical development programs, and manufacturing-related activities. Total operating expenses for the second quarter ended June 30, 2019 were $51.1 million, compared to $40.6 million for the same period in 2018. Research and development expenses were $36.5 million for the second quarter of 2019, compared to $29.3 million for the same period in 2018. The increase was primarily due to manufacturing and clinical trial expenses related to the progress of the Company’s clinical development programs. General and administrative expenses were $14.6 million for the second quarter of 2019, compared to $11.3 million for the same period in 2018. The increase was primarily due to increased compensation costs related to headcount growth and increased facility expenses, primarily related to our new Brisbane facility.

Financial Guidance for 2019

Operating Expense: Sangamo expects operating expense of $210 to $220 million for the year ending December 31, 2019.

Cash and Investments: Sangamo projects that current cash, cash equivalents, and investments should provide funds for operations through year end 2021.

Conference Call

Sangamo will host a conference call today, August 7, 2019, at 5:00 p.m. Eastern Time, which will be open to the public. The call will also be webcast live and can be accessed via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations.

The conference call dial-in numbers are (877) 377-7553 for domestic callers and (678) 894-3968 for international callers. The conference ID number for the call is 9582057. A conference call replay will be available for one week following the conference call. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 9582057.

On August 6, 2019 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported business highlights and financial results for the second quarter ended June 30, 2019 (Press release, Fate Therapeutics, AUG 6, 2019, View Source [SID1234538189]).

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 early safety and tolerability signals observed in patients receiving multiple doses of FT500, the first iPSC-derived cell therapy to undergo clinical investigation in the United States, are very encouraging. The ability to cost-effectively mass-produce a universal cell-based cancer immunotherapy, and to safely deliver that therapy ‘on demand’ in multiple doses, has the potential to transform outcomes for many patients," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We continue to be very pleased with the Company’s rapid pace of innovation, product development and leadership in bringing iPSC-derived cell-based immunotherapies engineered with potent anti-tumor functionality to cancer patients. Our first engineered iPSC-derived NK cell product candidate, FT516, is ready for Phase 1 clinical evaluation following successful completion of cGMP production, and the IND application for our multi-antigen targeted CAR19 NK cell product candidate, FT596, has been submitted to the FDA. Additionally, with the renewal of our collaboration with Memorial Sloan Kettering Cancer Center for the development of iPSC-derived T-cell immunotherapies, we are well positioned to continue to lead the field in the development of off-the-shelf CAR T-cell therapy."

Universal, Off-the-Shelf NK Cell Cancer Immunotherapy Clinical Programs

No DLTs Reported at 300M Cell Dose Level in FT500 Monotherapy Arm. The first three patients with advanced solid tumors have been treated with multiple doses of FT500, the Company’s universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line, at the second dose level in the study’s monotherapy arm. All three patients received three weekly doses of FT500 at 300 million cells per dose in an outpatient setting, which treatment cycle was well-tolerated with no dose-limiting toxicities (DLTs) and no FT500-related serious adverse events reported by investigators. All three subjects were eligible to receive a second, multi-dose treatment cycle of FT500 at 300 million cells per dose.
No DLTs Reported at 100M Cell Dose Level in FT500 ICI Combination Arm. The first three patients with advanced solid tumors have been treated with multiple doses of FT500 in combination with immune checkpoint inhibitor (ICI) in the study’s combination arm. All three patients received three weekly doses of FT500 at 100 million cells per dose in an outpatient setting, which treatment cycle was well-tolerated with no dose-limiting toxicities and no FT500-related serious adverse events reported by investigators. All three subjects were eligible to receive a second, multi-dose treatment cycle of FT500 at 100 million cells per dose in combination with ICI.
FT516 cGMP Production Completed and Product Released for Clinical Trial Initiation. The Company completed final product release testing for FT516, a universal, off-the-shelf NK cell product candidate derived from a clonal master iPSC line engineered to express a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor. Starting with a single cryopreserved vial from a master engineered iPSC bank, hundreds of cryopreserved doses of FT516 were produced in a single cGMP campaign at a low cost per dose. The cryopreserved FT516 cell product met stringent post-thaw release specifications, including identity, purity, viability and functional activity. The Company is currently initiating clinical investigation of FT516 as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-directed monoclonal antibodies for the treatment of B-cell lymphoma. FT516 is the first-ever cell product in the world derived from a genetically engineered pluripotent stem cell to be cleared for clinical investigation.
Universal, Off-the-Shelf NK Cell and T-cell Cancer Immunotherapy Preclinical Pipeline

Submitted IND for FT596 Multi-Antigen Targeted CAR NK Cell. FT596 is the Company’s first universal, off-the-shelf chimeric antigen receptor (CAR) NK cell product candidate, and is uniquely designed to engage multiple tumor-associated antigens expressed on cancer cells for best-in-class activity. The product candidate is derived from a master iPSC line engineered to express three functional anti-tumor components: a proprietary CAR targeting the B-cell antigen CD19; a novel hnCD16 Fc receptor for augmented antibody-dependent cellular cytotoxicity; and a unique IL-15 receptor fusion for enhanced NK cell activity. The Company submitted its Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for clinical investigation of FT596 as a monotherapy and in combination with monoclonal antibody therapy for the treatment of subjects with advanced B-cell lymphomas and advanced chronic lymphocytic leukemia.
Renewed iPSC-derived T-cell Collaboration with MSK. Under its collaboration with Memorial Sloan Kettering Cancer Center (MSK) led by Michel Sadelain, M.D., Ph.D., Director of the Center for Cell Engineering and the Stephen and Barbara Friedman Chair, the Company is currently conducting IND-enabling activities for FT819, its first universal, off-the-shelf CAR T-cell product candidate. FT819 is derived from a clonal master engineered iPSC line having complete elimination of T-cell receptor (TCR) expression and insertion of a novel 1XX CAR targeting CD19 into the T-cell receptor alpha (TRAC) locus. The three-year renewal extends the Company’s exclusive collaboration with Dr. Sadelain for the research and development of iPSC-derived T-cell product candidates.
Corporate Highlights

Received New U.S. Patent for CAR-encoded iPSCs. In May 2019, the U.S. Patent and Trademark Office granted to the Company a patent foundational to off-the-shelf, iPSC-derived CAR T-cell therapy. U.S. Patent Number 10,287,606, entitled "Genomic Engineering of Pluripotent Cells," covers iPSCs having a CAR construct encoded into the TRAC locus and an endogenous TCR alpha gene knocked out. The complete elimination of the endogenous TCR gene is critical in allogeneic CAR T-cell therapy to ensure the prevention of graft-versus-host disease, a life-threatening disease that can occur when donor T-cells attack a patient’s healthy tissue.
Expanded Board of Directors. In July 2019, the Company appointed Dr. Shefali Agarwal to its Board of Directors. Dr. Agarwal has nearly two decades of leadership experience across clinical development, medical research, clinical operations, regulatory, and medical affairs in oncology, and is currently the Chief Medical Officer of Epizyme, Inc., a clinical-stage company developing novel epigenetic therapies for cancer and other serious diseases.
Second Quarter 2019 Financial Results

Cash & Short-term Investment Position: Cash, cash equivalents and short-term investments as of June 30, 2019 were $162.0 million, compared to $201.0 million as of December 31, 2018. The decrease was driven primarily by the Company’s use of cash to fund operating activities.
Total Revenue: Revenue was $2.8 million for the second quarter of 2019, compared to $1.0 million for the same period in 2018. Revenue was derived primarily from the Company’s collaboration with Ono Pharmaceutical.
R&D Expenses: Research and development expenses were $21.6 million for the second quarter of 2019, compared to $16.8 million for the same period in 2018. The increase in R&D expenses was attributable primarily to an increase in employee compensation, including share-based compensation, and in expenses associated with the clinical development and manufacture of the Company’s product candidates and the conduct of our research activities including under our collaboration agreements.
G&A Expenses: General and administrative expenses were $5.3 million for the second quarter of 2019, compared to $3.8 million for the same period in 2018. The increase in G&A expenses was attributable primarily to an increase in employee compensation, including share-based compensation.
Shares Outstanding: Common shares outstanding were 65.3 million as of June 30, 2019 and 64.7 million as of December 31, 2018. Preferred shares outstanding as of June 30, 2019 and December 31, 2018 were 2.8 million, each of which is convertible into five shares of common stock.
Today’s Conference Call and Webcast
The Company will conduct a conference call today, Tuesday, August 6, 2019 at 5:00 p.m. ET to review financial and operating results for the quarter ended June 30, 2019. In order to participate in the conference call, please dial 877-303-6235 (domestic) or 631-291-4837 (international) and refer to conference ID 3898842. The live webcast can be accessed under "Events & Presentations" in the Investors & Media section of the Company’s website at www.fatetherapeutics.com. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered in repeat doses to mediate more effective pharmacologic activity, including in combination with cycles of other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is fraught with batch-to-batch and cell-to-cell variability that can affect safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 200 issued patents and 150 pending patent applications.

About FT500
FT500 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line. Despite the clinical benefit conferred by approved immune checkpoint inhibitor (ICI) therapy against a variety of tumor types, these therapies are not curative and, in most cases, patients either fail to respond or progress on these agents. One common mechanism of resistance to ICI therapy is associated with loss-of-function mutations in genes critical for antigen presentation. A potential strategy to overcome resistance is through the administration of allogeneic NK cells, which have the inherent capability to recognize and directly kill tumor cells with these mutations. FT500 is being investigated in an open-label, multi-dose Phase 1 clinical trial for the treatment of advanced solid tumors (clinicaltrials.gov ID number NCT03841110). The study is designed to assess the safety and activity of three once-weekly doses of FT500 as a monotherapy and in combination with one of three FDA-approved ICI therapies – nivolumab, pembrolizumab or atezolizumab – in patients that have failed prior checkpoint inhibitor therapy. Patients who are clinically stable following the first cycle of FT500 treatment are eligible to receive a second treatment cycle of three additional once-weekly doses of FT500.

About FT516
FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity (158V), non-cleavable CD16 (hnCD16) Fc receptor. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. CD16 occurs in two variants, either with high (158V) or low (158F) affinity for the Fc domain of IgG1 antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the CD16 high-affinity variant, which is present in approximately 15% of patients, have improved clinical outcomes. In addition, ADCC is dependent on NK cells maintaining active levels of CD16 expression, and the expression of CD16 on NK cells has been shown to undergo considerable down-regulation in cancer patients, which can significantly inhibit anti-tumor activity. FT516 incorporates a novel CD16 Fc receptor, which has been modified to prevent its down-regulation and augment its binding to tumor-targeting antibodies for enhanced ADCC. The FDA has allowed investigation of FT516 in an open-label, multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-directed monoclonal antibodies for the treatment of B-cell lymphoma (clinicaltrials.gov ID number NCT04023071).