On March 5, 2018 G1 Therapeutics, Inc. (Nasdaq: GTHX), a clinical-stage oncology company, reported positive topline data from its Phase 2a trial evaluating trilaciclib in patients undergoing chemotherapy for first-line small cell lung cancer (SCLC) (Press release, G1 Therapeutics, MAR 5, 2018, View Source [SID1234524392]). Trilaciclib is a potential first-in-class short-acting CDK4/6 inhibitor in development to preserve hematopoietic stem cells and enhance immune system function (myelopreservation) during chemotherapy.

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 data from this trial showed clear evidence that trilaciclib preserved bone marrow and immune system function from the damaging effects of chemotherapy," said Raj Malik, M.D., Chief Medical Officer and Senior Vice President, R&D. "Moreover, the myelopreservation effects demonstrated by trilaciclib improved patient outcomes. Chemotherapy continues to be a cornerstone of cancer treatment, and trilaciclib has the potential to benefit many of these patients."

Trial Design

This double-blind, placebo-controlled trial enrolled participants with a confirmed diagnosis of extensive-stage SCLC. The trial randomized 77 treatment-naïve participants in a 1:1 ratio, and 75 received trilaciclib or placebo administered intravenously prior to each dose of standard-of-care etoposide and carboplatin (EP) chemotherapy. Participants in both arms of the trial were able to receive standard supportive care as recommended by the trial investigator. Growth factors, including granulocyte colony-stimulating factor (G-CSF) and erythropoietin, and transfusion support were available to all participants. The statistical analysis plan prospectively defined several clinically-relevant hematologic endpoints.

Key Trial Findings

Data from this signal-generating Phase 2a trial demonstrated that trilaciclib reduced clinically relevant consequences of chemotherapy-induced myelosuppression versus placebo. Trilaciclib was well tolerated, with no Grade 3/4 trilaciclib-related treatment emergent adverse events (TEAEs) reported. Baseline demographics and disease characteristics were generally well balanced between the two arms. Key hematological results are shown in the table below.

1

Parameter

EP (1) + placebo
Patients
N = 37 EP + trilaciclib
Patients
N = 38 %
Reduction P-
value (2)
Patients with Gr 3/4 Hematologic TEAEs

27 (73.0%) 9 (23.7%) 67.5 % <0.0001
Patients with Gr 3/4 Neutropenia

30 (81.1%) 15 (39.5%) 51.3 % 0.0002
Patients with Gr 4 Neutropenia

16 (43.2%) 2 (5.3%) 87.7 % 0.0001
Patients with Gr 4 Neutropenia in Cycle 1

13 (35.1%) 1 (2.6%) 92.6 % 0.0003
Cycles with Febrile Neutropenia

5 1 80.8 % 0.1542
Patients with Febrile Neutropenia

3 (8.1%) 1 (2.6%) 67.9 % 0.2773
Patients with G-CSF Administration

24 (64.9%) 4 (10.5%) 83.8 % <0.0001
Patients with Chemotherapy Cycle Delays

25 (67.6%) 15 (39.5%) 41.6 % 0.0170
Patients with Chemotherapy Dose Reductions

13 (35.1%) 3 (7.9%) 77.5 % 0.0033

(1) etoposide and carboplatin
(2) significance testing at two-sided alpha = 0.2 per prospectively defined analysis plan
The trilaciclib arm also showed favorable trends with reduced Grade 3 anemia, red blood cell transfusions, and Grade 3 thrombocytopenia versus placebo. There was no Grade 4 anemia or thrombocytopenia in either arm.

In addition to demonstrating myelopreservation benefits across multiple hematopoietic lineages, trilaciclib showed favorable trends versus placebo for overall response rate (ORR), duration of response (DOR) and progression free survival (PFS). The survival data are still immature.

• ORR by blinded independent central review (BICR): trilaciclib 66.7%, placebo 62.2% (p=0.6759)

• Median DOR (BICR): trilaciclib 5.7 months, placebo 4.3 months (p=0.1449)

• PFS (investigator, including clinical progression) median: trilaciclib 6.2 months, placebo 5.0 months (hazard ratio 0.6, p=0.06)
The company plans to share these data with U.S. and European regulatory authorities this year and discuss next steps for the development of trilaciclib. The company also plans to present results from this trial, including updated data from the Phase 1b portion, at a medical meeting later this year.

G1 is currently conducting two additional clinical trials of trilaciclib to assess myelopreservation in second- / third-line SCLC and first- / second- / third-line triple-negative breast cancer, with preliminary data from both trials expected in the fourth quarter of 2018. In addition to myelopreservation, trilaciclib’s effect on overall survival (OS) is being evaluated in a Phase 2a trial in first-line extensive stage SCLC as part of a combination regimen with Tecentriq / carboplatin / etoposide. Enrollment of that trial was completed last month, two quarters ahead of schedule.

"The strength of this dataset provides us with a solid foundation to advance the development of trilaciclib and its ultimate commercialization," said Mark Velleca, M.D., Ph.D., Chief Executive Officer. "As shown by our non-exclusive collaboration with Genentech, there is significant interest in combining trilaciclib with checkpoint inhibitor / chemotherapy regimens. We believe that trilaciclib has the potential to become backbone therapy for multiple chemotherapeutic regimens across a variety of cancer types, delivering significant benefits to patients and creating a substantial long-term commercial opportunity."

2

Webcast and Conference Call

The G1 management team will host a conference call and webcast at 8 a.m. EST today. The live call may be accessed by dialing 866-763-6020 (domestic) or 210-874-7713 (international) and entering the conference code: 3098523. A live and archived webcast will be available in the Investors section of G1’s website at www.g1therapeutics.com.

About Trilaciclib (G1T28)

Trilaciclib is a potential first-in-class short-acting CDK4/6 inhibitor in development to preserve hematopoietic stem cells and enhance immune system function during chemotherapy. Trilaciclib is administered intravenously prior to chemotherapy and has the potential to significantly improve treatment outcomes.

Trilaciclib is being evaluated in four randomized Phase 2 clinical trials: a trial in newly diagnosed, treatment-naive SCLC patients (NCT02499770), a trial in previously treated SCLC patients (NCT02514447), a trial in patients with triple-negative breast cancer (NCT02978716), and a trial in combination with Tecentriq and chemotherapy in SCLC patients (NCT03041311).

On March 5, 2018 Aduro Biotech, Inc. (NASDAQ:ADRO) reported that the company earned a $3.0 million development milestone payment under its worldwide licensing agreement with Merck (known as MSD outside the United States and Canada) for the initiation of a Phase I clinical trial of its anti-CD27 antibody (Press release, Aduro Biotech, MAR 5, 2018, View Source;p=RssLanding&cat=news&id=2336295 [SID1234524377]). The Phase 1 trial is designed to evaluate the safety and pharmacokinetics of the anti-CD27 antibody when administered alone and in combination with pembrolizumab in adults with advanced solid tumors.

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 are pleased with the strong progress Merck has made in the development of our anti-CD27 antibody," stated Hans van Eenennaam, Ph.D., executive vice president of antibody research and site head, Aduro Biotech Europe. "This marks an important step forward in the advancement of our proprietary B-select monoclonal antibody technology, as the second antibody to enter the clinic."

About CD27 and Aduro’s Anti-CD27 Antibody
CD27 is a co-stimulatory receptor expressed on different immune cells, such as T-lymphocytes and NK (natural killer) cells. It has been recognized as having an important role in priming, enhancing and sustaining a productive anti-cancer (CD8 T-cell) adaptive immune response. In preclinical studies, anti-CD27 activation was shown to enhance T-cell response, which in combination with immune checkpoint inhibition demonstrated the ability to achieve complete tumor eradication.

In 2014, Merck, through certain affiliates, entered into a worldwide license agreement for the development and commercialization of CD27 antibody agonists. Aduro’s anti-CD27 antibody, which was identified with its proprietary B-select monoclonal antibody technology, targets a functional epitope on CD27 demonstrating potent activation of the CD27 co-stimulatory pathway in pre-clinical studies. As a part of the worldwide license agreement, and in addition to payments received, including the $15 million up-front payment, Aduro is eligible to receive future development, commercial and net sales milestone payments. In addition, Aduro is eligible to receive royalties in the mid-single digits to low teens based on any net sales of the product, if it is approved for marketing.

On March 5, 2018 Conatus Pharmaceuticals Inc. (NASDAQ:CNAT) reported that, at three upcoming investor conferences in March, President, Chief Executive Officer and co-founder, Steven J. Mento, Ph.D., and Conatus Executive Vice President, Chief Operating Officer and Chief Financial Officer, Keith W. Marshall, Ph.D., M.B.A., will focus on the company’s expected announcements of clinical trial results (Press release, Conatus Pharmaceuticals, MAR 5, 2018, View Source [SID1234524367]).

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 intend to use the upcoming conferences to provide context for our four planned data readouts, the first being the announcement of top-line results from our POLT-HCV-SVR trial in the second quarter," said Dr. Mento. "This randomized, placebo-controlled Phase 2b trial is evaluating two years of treatment with emricasan, our first-in-class pan-caspase inhibitor, in post-orthotopic liver transplant (POLT) recipients with liver fibrosis or cirrhosis post-transplant as a result of recurrent hepatitis C virus (HCV) infection who have successfully achieved a sustained viral response (SVR) following HCV antiviral therapy."

"In collaboration with Novartis, we expect to announce top-line results from four ongoing Phase 2b clinical trials in 2018 and 2019, including the POLT-HCV-SVR trial, two trials in nonalcoholic steatohepatitis (NASH) cirrhosis, and one in NASH fibrosis," said Dr. Marshall. "We are also advancing with our independent pipeline expansion activities and expect to provide further updates later this year. We believe our current financial resources, together with the anticipated reimbursements for 50% of the costs for the four ongoing clinical trials, without including any potential milestone payments under the Novartis collaboration, are sufficient to maintain operations through top-line results from all four Phase 2b clinical trials by the end of 2019, as well as to fund initial pipeline expansion activities."

At the Roth Capital Partners 30th Annual Conference (March 11-14 in Laguna Niguel, CA), Dr. Mento will participate in two panel discussions on NASH cirrhosis on Monday, March 12, as part of the integrated Spring NASH Bash. Dr. Mento and Dr. Marshall will meet with investment professionals and will provide an overview and update presentation beginning at 1:30 p.m. ET on Monday, March 12.

At the H.C. Wainwright 2nd Annual NASH Investor Conference (March 19 in New York), Dr. Marshall will present a NASH-focused presentation beginning at 3:40 p.m.

At the Oppenheimer Healthcare Conference (March 20-21 in New York), Dr. Mento and Dr. Marshall will meet with investment professionals and will provide an overview and update presentation beginning at 10:20 a.m. ET on Wednesday, March 21. An audio webcast and copy of the Oppenheimer conference presentation will be available in the Investors section of the company’s website at www.conatuspharma.com.

On March 5, 2018 VistaGen Therapeutics Inc. (NASDAQ: VTGN), a clinical-stage biopharmaceutical company developing new generation medicines for depression and other central nervous system (CNS) disorders, reported that Shawn Singh, Chief Executive Officer, will present at Oppenheimer’s 28th Annual Healthcare Conference in New York City at 8:00 a.m. Eastern Time on Wednesday, March 21, 2018 (Press release, VistaGen Therapeutics, MAR 5, 2018, View Source [SID1234524424]).

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!

For more information about the conference, or to schedule a one-on-one meeting with VistaGen’s management, please contact your Oppenheimer representative directly, or visit the conference website: View Source

On March 5, 2018 Kitov Pharmaceuticals (NASDAQ: KTOV; TASE: KTOV), an innovative biopharmaceutical company, reported that it filed its Annual Report for 2017 on Form 20-F, including its full financial results for the year ended December 31, 2017 (Press release, Kitov Pharmaceuticals , MAR 5, 2018, View Source [SID1234524417]).

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!

Kitov also today released a Letter from Chief Executive Officer, Isaac Israel, regarding recent activities and plans:

"Dear Shareholders,

Following the publication of our Annual Report for 2017, I would like to share with you our major accomplishments during 2017 and our plans and expectations for 2018.

HIGHLIGHTS OF 2017:

Consensi

Our team made important progress on our lead drug candidate, Consensi (which we formerly referred to as KIT-302).

Consensi, a combination drug that simultaneously treats pain caused by osteoarthritis and treats hypertension, is comprised of two FDA approved drugs, celecoxib (Celebrex), an NSAID, for the treatment of pain caused by osteoarthritis, and amlodipine besylate (Norvasc), a drug designed to treat hypertension. Hypertension is one of the side effects of using non-steroidal anti-inflammatory drugs, or NSAIDs, including celecoxib. Approximately 50% of the patients suffering from osteoarthritis in the US also suffer from hypertension, so industry sources estimate there are millions of patients that suffer from both conditions.

We made advances in several important areas:

Regulatory: The FDA filed our New Drug Application (NDA) for Consensi, following our submission of the NDA. We are very proud of the high-quality NDA package that was filed by the FDA. The FDA has set a PDUFA date of May 31, 2018 for Consensi.

Positive Clinical Trial Results: We announced the top-line results of our Phase III/IV randomized double-blind, placebo-controlled renal function clinical trial for Consensi. These results successfully validated the primary efficacy endpoint of our earlier successfully completed Phase III clinical trial. As such, we now have additional clinical evidence that establishes that adding celecoxib to amlodipine does not impair the blood pressure lowering effects of amlodipine. The trial also increased the total number of patients treated with Consensi, which we believe could increase the probability of ultimately receiving marketing approval for Consensi from the FDA.

Moreover, the Phase III/IV study strengthened the clinical evidence of the positive effect of Consensi on kidney function, which could provide us with a significant marketing advantage in the future.

Most importantly, we have advanced towards our goal of providing a safer NSAID, with the potential to be the first and only NSAID in the market which is both effective in lowering blood pressure and reduces the risk of kidney damage.

Commercial Partnership: We signed a definitive License Agreement for Consensi with Kuhnil Pharmaceutical Co. Ltd., a leading South Korean pharmaceutical company, for the territory of South Korea. Kuhnil will bear responsibility for and the costs of seeking regulatory approval for Consensi in South Korea. Under the terms of the agreement, we are entitled to receive payments upon achievement of certain predefined regulatory milestones, as well as double-digit royalties on net sales. Our relationship with Kuhnil and preparations for commercial launch in South Korea are proceeding as planned, and we have received our first milestone payment from Kuhnil.

South Korea is an important, attractive, gateway market into Asia, and we are very pleased with our choice of Kuhnil, which has the organizational and marketing infrastructure and capabilities for a successful commercial launch, which is expected to occur in 2019.

Patent Protection: We received a Notice of Allowance from the U.S. Patent & Trademark Office (USPTO) related to claims expanding the patent coverage of Consensi to include oral dosage compositions containing both amlodipine and celecoxib. The Notice of Allowance should result in the issuance of an additional patent that would further strengthen Kitov’s proprietary position and long-term U.S. market exclusivity for Consensi.

TyrNovo: NT219 – Small molecule oncology drug

We acquired a majority stake in TyrNovo, a private oncology company, which is developing NT219, a small molecule drug that presents a new and exciting concept in cancer therapy by attempting to address a major problem whose solution has been elusive to date – tumors’ developing cancer-drug resistance. NT219 is a unique compound that is designed to prevent and reverse resistance to anti-cancer drugs through dual inhibition of STAT3 and IRS1/2, two signal pathways associated with drug resistance. Kitov’s current ownership in TyrNovo is 65% and we have a pending transaction to increase our stake in TyrNovo to approximately 92%, expected to be closed in the next few weeks.

We are very pleased with this acquisition, its progress during 2017 and, most importantly, its long-term potential. NT219 has demonstrated impressive efficacy in large array of pre-clinical models with several leading targeted oncology drugs, with chemotherapy drugs and with Immuno-Oncology drugs in various cancer types, including in combination with Keytruda. Our development program is of critical importance, as we prepare for the start of human clinical trials in 2019.

Furthermore, we received the FDA’s response to NT219’s pre-IND meeting package. In its response, the FDA agreed to our preclinical and clinical development plans for NT219, and we are considering the initiation of clinical studies in combination with gemcitabine (Gemzar) for the treatment of pancreatic cancer and/or in combination with osimertinib (TagrissoTM) for the treatment of non-small cell lung cancer (NSCLC).

Our goal is to develop NT219 in combination with approved oncology drugs to increase efficacy, expand target populations and treatment duration. Our long-term strategy is to develop NT219 in combination with other oncology drugs and for additional oncology indications, on our own or in collaboration with potential strategic partners. Our preliminary partnering discussions for NT219 have yielded positive feedback, and this will be a focus area for TyrNovo throughout 2018.

OUTLOOK FOR 2018

Our major goals for 2018 are:

●To submit to the FDA our study report for the recently completed Phase III/IV renal function clinical trial for Consensi. We believe the clinical study report is of major significance in that it could strengthen the drug’s labeling and support future marketing of Consensi.

●Receive marketing approval for Consensi from the FDA.

●To successfully expand our business development efforts for Consensi by entering into additional distribution or licensing agreements in the U.S. and other target markets, with an emphasis on China and other countries in Asia.

●Make significant progress towards finalizing the submission of an IND application for NT219 to the FDA in order to pave the way for the start of clinical trials in 2019.

●Continue to strengthen our patent protection for both Consensi and NT219 through the submission of various patent applications and the expansion of our existing patent families.

I want to thank you, our shareholders, for the trust you have placed in us. Our board of directors and management team is committed to continuing to unlock the substantial value in our business by leveraging our team’s deep regulatory expertise and drug development experience, complemented by targeted business development efforts, in order to maximize the potential of our therapeutic candidates.

This past year has taught us all at Kitov a great deal about our team’s special human qualities and its determination, dedication, and commitment to face any challenge.

We look forward to providing you with further updates on our continued progress throughout 2018.

Best wishes for a successful year.

Kind regards,
Mr. Isaac Israel
Chief Executive Officer"