On November 4, 2019 MAX BioPharma, Inc. (www.maxbiopharma.com) reported that published two articles describing its anti-tumorigenic oxysterol lead compounds in the peer-reviewed journal, Cells (Press release, MAX BioPharma, NOV 4, 2019, View Source [SID1234550237]). Oxy186 (View Source) and Oxy210 (View Source) are derived from the Company’s Oxysterol Therapeutics platform of proprietary oxysterols. MAX BioPharma is currently optimizing the compounds for oral dosing and performing pre-clinical studies required by the FDA for clinical development and commercialization.

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MAX BioPharma’s anti-tumorigenic oxysterol, Oxy186, inhibits the Hedgehog signaling pathway, which is dysregulated and activated in many human tumors including pancreatic and lung cancers. Oxy210, an analogue of Oxy186, inhibits Hedgehog signaling as well as transforming growth factor (TGF)beta signaling. Oxy210 and Oxy186 have unique mechanisms of action compared to other Hedgehog and TGFbeta signaling inhibitors that are commercially available or under clinical development. MAX BioPharma is focusing its efforts to develop these compounds for lung and pancreatic cancers, which still have huge unmet medical needs. Oxy210 and Oxy186 have favorable pharmacokinetic and safety profiles, are scalable, and were found to inhibit tumor cell growth, invasive activity, and epithelial-mesenchymal transition, a hallmark of cancer metastasis. In addition, Oxy210 was found to inhibit development of chemoresistance by tumor cells and to enhance the cytotoxic effects of carboplatin on lung cancer cells in vitro.

MAX BioPharma has collaborated with Dr. Ying Zhang of the National Cancer Institute (NCI) under a Materials-Cooperative Research and Development Agreement (M-CRADA) and with academic investigators. These collaborations are evaluating the potential of the oxysterols to be potent, orally bioavailable, and safe therapies for cancer. "Given the important role of Hedgehog signaling in acute myeloid leukemia (AML) and the recent FDA approval of a Hedgehog pathway inhibitor, DaurismoTM (glasdegib) by Pfizer, for the treatment of AML, we are excited to begin examining the potential of oxysterols for targeting AML" explains Dr. William Matsui, co-founder of MAX BioPharma and Professor of Oncology and Deputy Director of LIVESTRONG Cancer Institutes at the University of Texas in Austin. MAX BioPharma is seeking strategic partnerships with biotechnology and pharmaceutical companies that have the expertise and resources to further the development of oxysterols as a cancer therapeutic towards FDA approval and commercialization. In addition, MAX BioPharma is in the process of raising a series A financing round to support the advancement of its therapeutic development programs. "We are extremely excited about the progress of our oncology program and we believe that our findings will be groundbreaking in finding more effective cures for cancer," says Dr. Farhad Parhami, President & CEO of MAX BioPharma.

On November 4, 2019 Revolution Medicines, Inc., a clinical-stage oncology company focused on developing targeted therapies to inhibit elusive frontier targets within notorious cancer pathways, reported an agreement with Amgen to evaluate the combination of RMC-4630, the company’s investigational SHP2 inhibitor, and AMG 510, Amgen’s investigational KRASG12C inhibitor (Press release, Revolution Medicines, NOV 4, 2019, View Source [SID1234550253]). Amgen will conduct a Phase 1b clinical trial evaluating the safety, tolerability, pharmacokinetics, and efficacy of AMG 510 in combination with RMC‑4630 in subjects with advanced solid tumors harboring the KRASG12C mutation. Revolution Medicines will provide Amgen with clinical supply of RMC-4630 for the planned study.

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RMC-4630 and AMG 510 are selective investigational inhibitors of oncogenic targets at distinct positions within the RAS signaling cascade that are frequently exploited by human cancers. RMC-4630 is a potent and orally bioavailable small molecule that is designed to selectively inhibit the activity of SHP2, an upstream cellular protein that plays a key role in modulating cell growth by transmitting signals from receptor tyrosine kinases to RAS. RMC-4630 and SHP2 are the focus of an exclusive global research, development and commercialization agreement with Sanofi. AMG 510 is designed to selectively and irreversibly target the KRASG12C protein, an oncogenic RAS mutant at the core of the RAS signaling cascade.

Preclinical and clinical research has shown that cancers caused by KRASG12C and other RAS pathway mutations exhibit "oncogene addiction," in which tumor cells are highly dependent on RAS pathway signaling to survive. Such tumors can develop adaptive resistance by hijacking cell signaling circuitry to circumvent pathway inhibitors and restore RAS signaling. The planned clinical Phase 1b study is the first step in evaluating whether inhibition of the RAS pathway at two nodes simultaneously through the combination of RMC-4630 and AMG 510 increases the depth or durability of clinical benefit for patients with tumors bearing KRASG12C.

"We and our partner Sanofi are committed to a clinical strategy that includes exploring in-pathway combinations including RMC-4630 to optimize treatment options for patients with RAS-dependent tumors. This collaboration with Amgen, a clinical pioneer in the field, provides another opportunity to leverage RMC-4630," said Mark A. Goldsmith, M.D., Ph.D., president and chief executive officer of Revolution Medicines. "Our development program for RMC-4630 currently includes an ongoing Phase 1 monotherapy trial, an ongoing Phase 1b/2 study evaluating a combination with cobimetinib, a MEK inhibitor, and a planned Phase 1b trial evaluating a combination with AMG 510, the leading investigational KRASG12C inhibitor."

About RMC-4630 and Sanofi Collaboration

RMC-4630 is currently being evaluated in a Phase 1 monotherapy clinical trial (RMC-4630-01) for a range of tumor types featuring specific, molecularly-defined oncogenic mutations, as well as a Phase 1b/2 study (RMC-4630-02) in combination with cobimetinib in patients with relapsed/refractory solid tumors displaying specific genomic mutations. The RMC-4630 program is the focus of an exclusive global research, development and commercialization agreement with Sanofi, under which Revolution Medicines received a $50 million upfront payment, and Sanofi agreed to reimburse the Revolution Medicines for substantially all research and all development costs for the joint SHP2 program. Sanofi received an exclusive worldwide license for global commercialization of any approved products targeting SHP2, subject to a U.S. co-promote right for Revolution Medicines. The companies have agreed to enter into a 50/50 profit and loss share arrangement in the U.S., and Revolution Medicines is entitled to receive tiered royalties on annual net sales ranging from high single digit to mid-teen percentages on sales in other markets. Revolution Medicines could also receive more than $500 million in development and regulatory milestone payments.

On November 4, 2019 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, reported financial results for the third quarter of 2019 (Press release, NanoString Technologies, NOV 4, 2019, View Source [SID1234550270]).

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Third Quarter Financial Highlights

Total product and service revenue of $26.3 million, 23% year-over-year growth
Instrument revenue of $8.0 million, including $2.2 million of GeoMx DSP instrument revenue, 48% year-over-year growth
Consumables revenue of $15.3 million, including $2.5 million of Prosigna IVD kits, 11% year-over-year growth
Service revenue of $3.1 million, 31% year-over-year growth
Collaboration revenue recognized of $4.3 million and cash received from collaborators of $4.5 million
Updated fiscal 2019 product and service revenue guidance to $100 to $103 million from the previous range of $98 to $103 million, which includes GeoMx DSP revenue guidance at the top end of the previous range
"During the third quarter we achieved the seventh consecutive quarter of double-digit revenue growth in our core nCounter business, driven by strong instrument placements and an expanded consumable portfolio," said Brad Gray, president and CEO of NanoString. "The shipment of our first commercial GeoMx DSP instruments during the third quarter accelerated our instrument revenue growth to more than 40%, and we see positive leading indicators of GeoMx interest including record demand for our GeoMx Technology Access Program."

Recent Business Highlights

nCounter Platform

Increased installed base to approximately 820 nCounter Analysis Systems at September 30, 2019, as compared to approximately 695 systems at September 30 in the prior year.
Surpassed 2,800 cumulative peer-reviewed publications of studies utilizing nCounter technology.
Launched nCounter Human Organ Transplant Panel to study the mechanisms of organ rejection and to monitor the toxicities of immunosuppressive drugs and viral infections.
GeoMx Digital Spatial Profiling (DSP) Platform

Received orders for more than 15 additional GeoMx DSP systems, bringing cumulative orders to more than 70 systems.
Shipped our first ten commercial GeoMx DSP systems during the quarter.
Completed more than 40 GeoMx DSP Technology Access Program (TAP) projects during the third quarter, expanding the total number of projects completed to approximately 170 projects for about 110 unique customers.
GeoMx DSP featured on the cover of the September issue of Clinical Cancer Research, highlighting an article describing research by Dr. David Rimm et al. from Yale University using GeoMx DSP (see accompanying image).
First peer-reviewed publication demonstrating the utility of GeoMx DSP in Neuroscience research.
Leadership

Announced the appointment of Mark Winham as senior vice president of Operations. Mr. Winham was previously vice president of Global Manufacturing for Life Technologies.
Announced the appointment of Don Kania Ph.D., to the Company’s Board of Directors. Dr. Kania was previously the CEO and president of FEI, a leading electron microscopy company.
Third Quarter Financial Results

Product and service revenue for the three months ended September 30, 2019 increased by 23% to $26.3 million, as compared to $21.5 million for the third quarter of 2018. Instrument revenue was $8.0 million, an increase of 48% compared to the prior year period. Consumables revenue, excluding Prosigna, was $12.7 million, an increase of 14% compared to the prior year period, with growth driven primarily by sales of our panel products. Prosigna IVD kit revenue remained flat at $2.5 million as compared to the prior year period. Service revenue was $3.1 million, an increase of 31% compared to the prior year period, reflecting continued growth in demand for our GeoMx DSP Technology Access Program and an increased number of service contracts associated with our growing installed base of nCounter instruments. Gross margin on product and service revenue was 59% compared to 57% in the prior year period, reflecting a mix shift towards our MAX and FLEX nCounter instruments as well as sales of our new GeoMx DSP instruments.

Collaboration revenue totaled $4.3 million, compared to $7.2 million for the prior year period, and was derived primarily from our collaboration with Lam Research. Cash received from collaborators totaled $4.5 million during the quarter, primarily reflecting activity relating to our collaboration with Lam Research and the remaining activities for our Celgene collaboration, which ended during the second quarter of this fiscal year.

Research and development expense increased by 2% to $17.0 million compared to $16.7 million for the prior year period, primarily due to higher stock-based compensation expense. Selling, general and administrative expense increased by 31% to $23.4 million compared to $17.8 million for the prior year period, primarily reflecting increased investment in personnel and commercial launch activities related to GeoMx DSP and higher stock-based compensation expense.

Net loss was $22.7 million, or a loss of $0.64 per share, compared with $16.5 million, or $0.56 per share, for the prior year period.

Outlook for 2019

The company updated its revenue and gross margin guidance for fiscal 2019, with results expected as follows:

Product and service revenue of $100 million to $103 million, including approximately $8 million of revenue recorded from sales of GeoMx DSP, as compared to previous guidance of $98 million to $103 million and $6 to $8 million respectively.
Total revenue of $121 million to $124 million, which includes product and service revenue plus approximately $21 million of collaboration revenue, as compared to previous guidance of $118 million to $123 million and approximately $20 million respectively.
Gross margin on product and service revenue of 58% to 59%, as compared to previous guidance of 57% to 59%.
The company also updated its guidance for certain operating expenses and other items. These updates reflect additional investments directed to capture demand for and support the launch of GeoMx DSP, as well as higher expected stock-based compensation expense. For the full year 2019, the company now expects:

Selling, general and administrative expenses of $92 million to $93 million, as compared to previous guidance of $85 million to $87 million.
Research and development expenses of $66 million to $67 million, as compared to previous guidance of $64 million to $66 million, to be partially offset by approximately $20 million expected to be received from Lam Research.
GAAP net loss of $85 million to $87 million, as compared to previous guidance of $78 million to $83 million.
Net loss per share of $2.40 to $2.50, as compared to previous guidance of $2.20 to $2.40, reflecting the collective impact of the updates described above and the impact of additional shares issued in the offering of common stock completed in March 2019.
Conference Call

Management will host a conference call today beginning at 1:30 pm PT / 4:30 pm ET to discuss these results and answer questions. Individuals interested in listening to the conference call may do so by dialing (866) 211-0364 for domestic callers, or (647) 689-6861 for international callers. Please reference Conference ID 9358402. To listen to a live webcast, please visit the investor relations section of the company’s website at www.nanostring.com. A replay of the call will be available beginning November 4, 2019 at 7:30 pm ET through midnight ET on November 11, 2019. To access the replay, dial (800) 585-8367 or (416) 621-4642 and reference Conference ID: 9358402. The webcast will also be available on the company’s website for one year following the completion of the call.

On November 4, 2019,UroGen Pharma Ltd. (the "Company") reported that it entered into a lease agreement, dated effective October 31, 2019 (the "Lease"), with Witman Properties, L.L.C., a New Jersey limited liability company, and Alexander Road at Davanne, L.L.C., a New Jersey limited liability company, as tenants in common (collectively, "Landlord"), for the lease of approximately 20,900 square feet of rentable area, which consists of the entire fourth floor of the building located at 400 Alexander Road, West Windsor, New Jersey 08540 constituting approximately 18,300 square feet of usable square footage (the "Premises") (Filing, 8-K, UroGen Pharma, NOV 4, 2019, View Source [SID1234550755]). The commencement date of the Lease (the "Commencement Date") is expected to be in the fourth quarter of 2019. The Company plans to use the Premises as its principal executive offices along with other general operating uses. The term of the Lease (the "Initial Term") is for 38 months after the Commencement Date. The Company has the option to renew the Lease for two additional periods of three years each (each additional period, a "Renewal Period"). The aggregate base rent due over the Initial Term is approximately $1.7 million. For the Renewal Periods, the rent due shall be the fair market value of the Premises at the time of the commencement of the Renewal Period multiplied by the rentable square footage of the Premises. The Company will also be responsible for the payment of additional rent to cover the Company’s share of the annual operating expenses of the building, subject to certain exceptions, and the annual tax expenses of the building. In the event of a default of certain of the Company’s obligations under the Lease, Landlord would have right to terminate the Lease and recover damages as provided by the lease contract and by law.

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On November 4, 2019 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported financial results for the third quarter ended September 30, 2019 (Press release, Mirati, NOV 4, 2019, View Source [SID1234550238]).

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Recent Corporate Updates:

Presented early clinical data from the Phase1/2 trial of MRTX849 on October 28, 2019 at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper). At the highest dose (600 mg BID), three of five (3/5) evaluable patients with non-small cell lung cancer (NSCLC) and one of two (1/2) evaluable patients with colorectal cancer (CRC) achieved a partial response (PR); the remaining patients had stable disease (SD). Across all dose levels, three of six (3/6) patients with NSCLC and one of four (1/4) patients with CRC achieved a PR. Two responding patients (1 NSCLC and 1 CRC) achieved confirmed PRs, both with continuing tumor shrinkage following their first scan. The other two patients with PRs (both NSCLC) have not had confirmatory scans. Clinical PK data demonstrated that the dose of 600 mg BID results in drug levels that meet or exceed those likely to lead to full inhibition of KRAS G12C signaling. Treatment duration ranged from 6.7- 38.6 weeks as of the data cut-off, October 11, 2019.

Published data demonstrating the efficacy of MRTX849 in preclinical studies on October 28, 2019 simultaneously with the Company’s oral presentations at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), in Cancer Discovery, a journal of the American Association of Cancer Researchers.

Announced that the Company would have two presentations of interim Phase 2 data for sitravatinib in combination with nivolumab in urothelial carcinoma and oral cavity squamous cell carcinoma at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting on November 9, 2019.

Announced on July 9, 2019 that the Company had entered into a clinical collaboration agreement with Novartis to evaluate the combination of MRTX849, Mirati’s investigational KRAS G12C inhibitor and TNO155, Novartis’ investigational SHP2 inhibitor, in patients with advanced solid tumors with KRAS G12C mutations.

"The recent data presented demonstrate that MRTX849 treatment can result in clinical responses at well tolerated doses. We believe that MRTX849 clinical combinations, including the combination of MRTX849 with TNO155 in our collaboration with Novartis, will significantly increase the eligible patient population," said Charles M. Baum, M.D., Ph.D., President and Chief Executive Officer at Mirati. "We continue to expand and accelerate our KRAS programs and expect to continue expanding our team, including the addition of commercial talent so that we are ready to deliver our novel cancer therapies to the patients most in need."

Financial Results for the Third Quarter 2019

Cash, cash equivalents, and short-term investments were $454.2 million at September 30, 2019, compared to $222.8 million at December 31, 2018. In January 2019, we completed a public offering of common stock that provided net cash proceeds of $107.9 million. In June 2019, we completed a public offering of common stock that provided net cash proceeds of $219.9 million.

License and collaboration revenues relate to the Collaboration and License Agreement between the Company and BeiGene, Ltd. ("BeiGene"), dated January 7, 2018. License and collaboration revenues for the three and nine months ended September 30, 2019 were $1.0 million and $2.8 million, respectively, compared to none and $9.5 million for the three and nine months ended September 30, 2018, respectively. The 2019 revenues relate to revenues earned in connection with a manufacturing supply services agreement with BeiGene and the 2018 revenues relate to the license the Company granted to BeiGene under the Collaboration and License Agreement.

Research and development expenses for the third quarter of 2019 were $47.4 million, compared to $23.6 million for the same period in 2018. Research and development expenses for the nine months ended September 30, 2019 were $119.9 million, compared to $67.1 million for the same period in 2018. The increase in research and development expenses is due to an increase in expense associated with the development of sitravatinib and MRTX849, as well as an increase in salaries and related expense, including an increase in share-based compensation expense. The Company recognized research and development-related share-based compensation expense of $8.6 million during the third quarter of 2019, compared to $1.8 million for the same period in 2018, and $20.4 million during the nine months ended September 30, 2019, compared to $5.1 million for the same period in 2018.

General and administrative expenses for the third quarter of 2019 were $10.7 million, compared to $5.3 million for the same period in 2018. General and administrative expenses for the nine months ended September 30, 2019 were $30.3 million, compared to $15.3 million for the same period in 2018. The increase is due primarily to an increase in share-based compensation expense and, to a lesser extent, an increase in employee related expense, professional services expense and facilities and insurance expense. The Company recognized general and administrative-related share-based compensation expense of $6.5 million during the third quarter of 2019, compared to $2.2 million for the same period in 2018, and $18.4 million during the nine months ended September 30, 2019, compared to $6.5 million for the same period in 2018.

Net loss for the third quarter of 2019 was $54.3 million, or $1.38 per share basic and diluted, compared to net loss of $27.6 million, or $0.85 per share basic and diluted for the same period in 2018. Net loss for the nine months ended September 30, 2019 was $140.9 million, or $3.83 per share basic and diluted, compared to net loss of $70.1 million, or $2.31 per share basic and diluted for the same period in 2018.

About Sitravatinib

Sitravatinib is an investigational spectrum-selective kinase inhibitor that potently inhibits receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, Mer), split family receptors (VEGFR2, KIT) and RET. As an immuno-oncology agent, sitravatinib is being evaluated in combination with nivolumab (OPDIVO), an anti-PD-1 checkpoint inhibitor, in patients whose cancers have progressed despite treatment with a checkpoint inhibitor. Sitravatinib’s potent inhibition of TAM and split family RTKs may overcome resistance to checkpoint inhibitor therapy through targeted reversal of an immunosuppressive tumor microenvironment, enhancing antigen-specific T cell response and expanding dendritic cell-dependent antigen presentation. Sitravatinib is being evaluated in multiple clinical trials to treat patients who are refractory to prior immune checkpoint inhibitor therapy, including the ongoing potentially registration-enabling Phase 3 trial of sitravatinib in combination with a checkpoint inhibitor in non-small

cell lung cancer (NSCLC). In addition, sitravatinib combinations with checkpoint inhibitors are being evaluated in selected checkpoint inhibitor naïve patients.

About MRTX849

MRTX849 is an investigational, orally-available small molecule that is designed to potently and selectively inhibit a form of KRAS which harbors a substitution mutation (G12C). KRAS G12C mutations are present in approximately 14% of non-small cell lung cancer adenocarcinoma patients, 4% of colorectal cancer patients, and subsets of other types of cancer. Tumors characterized by KRAS G12C mutations are commonly associated with poor prognosis and resistance to therapy, and patients with these mutations have few treatment options. MRTX849 is being evaluated in a Phase 1/2 trial treating patients with molecularly-identified, KRAS G12C-positive advanced solid tumors.