Kura Oncology Reports Fourth Quarter and Full Year 2020 Financial Results

On February 24, 2021 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported fourth quarter and full year 2020 financial results and provided a corporate update (Press release, Kura Oncology, FEB 24, 2021, View Source [SID1234575553]).

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"Last year was a transformative one for Kura, and our team continues to make tremendous progress advancing our pipeline of anti-cancer therapeutics," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "In December, we reported encouraging first-in-human data for our menin inhibitor KO-539 in an all-comers population of patients with acute myeloid leukemia (AML). Now, we look forward to obtaining a larger clinical dataset as we move into genetically enriched Phase 1 expansion cohorts comprising NPM1-mutant and KMT2A-rearranged relapsed/refractory AML patients. KO-539 continues to demonstrate a clean safety and tolerability profile, compelling clinical activity and a wide therapeutic window, supporting a potentially best-in-class profile both as a monotherapy and in combination."

"Meanwhile, we were very pleased to receive Breakthrough Therapy Designation from the FDA for tipifarnib," continued Dr. Wilson. "We believe this designation acknowledges both the dire unmet need for patients with recurrent or metastatic HRAS mutant HNSCC and the promise of tipifarnib to provide clinical benefit to patients. Breakthrough Therapy Designation is the latest milestone in our effort to pioneer the use of farnesyl transferase inhibitors to treat patients with cancer. We are also developing a next-generation farnesyl transferase inhibitor, which we intend to direct at innovative biology and larger oncology indications through rational combinations. We have identified multiple advanced lead compounds with superior properties, and we expect to nominate a development candidate for IND-enabling studies in mid-2021. Finally, thanks to a successful public offering in December, we are in a stronger financial position than ever before, and we believe this provides us with sufficient resources to advance our pipeline programs through multiple value-inflection points."

Recent Highlights

First clinical data for menin inhibitor KO-539 presented at ASH (Free ASH Whitepaper) – In December, Kura reported preliminary clinical data from a Phase 1/2 KOMET-001 clinical trial of KO-539 at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. These data were highlighted by single-agent activity in an all-comer population of patients with relapsed or refractory AML, including patients with NPM1 mutations and KMT2A rearrangements. KO-539 also demonstrated a favorable safety and tolerability profile, with no drug discontinuations due to treatment-related adverse events and no evidence of QTc prolongation.

KOMET-001 protocol amendment to include Phase 1 expansion cohorts – Kura is currently evaluating KO-539 in an 800 mg dose cohort in Phase 1 dose escalation, and KO-539 continues to demonstrate compelling clinical activity, encouraging safety and tolerability and a wide therapeutic window. Based on recent feedback from the FDA regarding the registration-enabling design for the KOMET-001 study, the Company is amending the trial protocol to include two Phase 1 expansion cohorts while continuing to evaluate KO-539 in dose escalation. Kura plans to enrich these Phase 1 expansion cohorts with NPM1-mutant and KMT2A-rearranged relapsed/refractory AML patients at doses that have already met the safety threshold to help determine a minimum safe and biologically effective dose. This will enable the Company to further characterize the efficacy of KO-539 in these target populations and better inform a recommended Phase 2 dose. Initiation of the genetically enriched Phase 1 expansion cohorts is expected in mid-2021.

Tipifarnib receives Breakthrough Therapy Designation from FDA – Earlier today, Kura announced that tipifarnib has been granted Breakthrough Therapy Designation by the FDA for the treatment of patients with recurrent or metastatic HRAS mutant head and neck squamous cell carcinoma (HNSCC) with variant allele frequency ≥ 20% after disease progression on platinum-based chemotherapy. The Breakthrough Therapy Designation is based upon data from the Company’s Phase 2 clinical trial (RUN-HN), which was recently accepted for publication in an upcoming issue of the Journal of Clinical Oncology. Tipifarnib is currently being evaluated in an ongoing registration-directed clinical trial (AIM-HN) in this indication of high unmet need.

Diagnostic development collaboration with Illumina – Kura recently entered into a strategic collaboration with Illumina to develop a diagnostic in support of Kura’s tipifarnib program. The partnership with Illumina is focused on the development of a next-generation sequencing-based companion diagnostic leveraging the content of TruSight Oncology 500 to detect HRAS mutations in HNSCC.

Initiation of Phase 1/2 study of tipifarnib plus PI3Kα inhibitor in 2H 2021 – In October, Kura reported preclinical data showing compelling activity of tipifarnib when combined with a PI3Kα inhibitor in models of HRAS-dependent and/or PI3K dependent HNSCC. The data, presented at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics, support the Company’s upcoming Phase 1/2 proof-of-concept study of tipifarnib in combination with a PI3Kα inhibitor in advanced or unresectable relapsed/refractory HNSCC harboring PIK3CA mutations or amplifications and/or HRAS overexpression. Kura believes that the total addressable population for tipifarnib may be as high as 50% of HNSCC.
Financial Results

Research and development expenses for the fourth quarter of 2020 were $17.5 million, compared to $13.5 million for the fourth quarter of 2019. Research and development expenses for the full year 2020 were $60.4 million, compared to $47.8 million for the prior year.

General and administrative expenses for the fourth quarter of 2020 were $8.8 million, compared to $5.5 million for the fourth quarter of 2019. General and administrative expenses for the full year 2020 were $31.5 million, compared to $19.7 million for the prior year.

Net loss for the fourth quarter of 2020 was $26.2 million, compared to a net loss of $17.9 million for the fourth quarter of 2019. Net loss for the full year 2020 was $89.6 million, compared to a net loss of $63.1 million for the prior year. Net loss for the fourth quarter and full year of 2020 included non-cash share-based compensation expense of $3.7 million and $12.8 million, respectively, compared to $2.4 million and $9.4 million for the same periods in 2019, respectively.

Cash, cash equivalents and short-term investments totaled $633.3 million as of December 31, 2020, compared with $236.9 million as of December 31, 2019. This includes net proceeds of approximately $324.1 million from a public offering completed in December 2020. Management expects that current cash, cash equivalents and short-term investments will be sufficient to fund current operations into 2024.
Upcoming Milestones

Initiation of genetically enriched Phase 1 expansion cohorts in KOMET-001 in mid-2021

Additional Phase 1 data from KOMET-001 in the second half of 2021

Initiation of a Phase 1/2 proof-of-concept study of tipifarnib in combination with a PI3Kα inhibitor in the second half of 2021

Nomination of a next-generation farnesyl transferase inhibitor Development Candidate in mid-2021
Conference Call and Webcast

Kura’s management will host a webcast and conference call at 8:00 a.m. ET / 5:00 a.m. PT today, February 24, 2021, to discuss the financial results for the fourth quarter and full year 2020 and provide a corporate update. The live call may be accessed by dialing (877) 516-3514 for domestic callers and (281) 973-6129 for international callers and entering the conference code: 8581798. A live webcast of the call will be available from the Investors and Media section of the Company’s website at www.kuraoncology.com, and will be archived there for 30 days.

Horizon Therapeutics plc Reports Record Fourth-Quarter and Full-Year 2020 Financial Results; Announces Full-Year 2021 Guidance

On February 24, 2021 Horizon Therapeutics plc (Nasdaq: HZNP) reported record fourth-quarter and full-year 2020 financial results and provided full-year 2021 net sales and adjusted EBITDA guidance (Press release, Horizon Pharma, FEB 24, 2021, View Source [SID1234575552]).

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"Our outperformance in 2020 capped off a breakthrough year for Horizon," said Tim Walbert, chairman, president and chief executive officer, Horizon. "The launch of TEPEZZA, one of the most successful rare disease medicine launches ever, strengthened our position as one of the fastest growing biotech companies. Our recently announced agreement to acquire Viela further strengthens this position by adding a deep mid-stage biologics pipeline and an on-market rare disease biologic, UPLIZNA. This significant progress allows us to build on the value we provide to patients and our shareholders."

Fourth-Quarter and Recent Company Highlights

Pending Acquisition of Viela Bio, Inc.: On Jan. 31, 2021, the Company entered into a definitive agreement to acquire Viela, a biotechnology company with a deep, mid-stage biologics pipeline for autoimmune and severe inflammatory diseases, an experienced R&D team and UPLIZNA, a recently approved biologic medicine for a rare disease. The acquisition represents a significant step forward in advancing the Company’s strategy to expand its pipeline to accelerate long-term sustainable growth by adding four pipeline candidates currently in nine development programs. Per the agreement, the Company will acquire all of Viela’s common stock for $53.00 per share in cash, which represents a fully diluted equity value of approximately $2.67 billion, net of Viela’s cash and cash equivalents. The transaction is expected to close by the end of the first quarter of 2021.

TEPEZZA Supply Update: In January 2021, the Company submitted a prior approval supplement to the U.S. Food and Drug Administration (FDA) to support increased scale production of TEPEZZA drug product for the treatment of Thyroid Eye Disease (TED). The submission includes data to support more drug product output with each manufacturing slot than is currently approved by the FDA. The Company will continue to discuss potential additional data requirements and the approval timeline with the FDA. The Company continues to expect that the disruption could last through the first quarter of 2021. As previously announced on Dec. 17, 2020, this increased production scale became necessary due to government-mandated COVID-19 vaccine production orders pursuant to the Defense Production Act of 1950 (DPA) that dramatically reduced the number of drug product production slots available to Horizon at the Company’s drug product contract manufacturer of TEPEZZA.

Entered into Agreement with Halozyme to Develop a TEPEZZA Subcutaneous (SC) Formulation: On Nov. 21, 2020, the Company and Halozyme Therapeutics, Inc. entered into a global collaboration and license agreement for exclusive access to Halozyme’s ENHANZE drug delivery technology for subcutaneous formulation of medicines targeting IGF-1R. The Company intends to use ENHANZE to develop a SC formulation of TEPEZZA, potentially shortening drug administration time, reducing healthcare practitioner time and offering additional flexibility and convenience for patients.

Completed Enrollment in KRYSTEXXA PROTECT Trial: In January 2021, the Company completed enrollment in the PROTECT open-label trial. The trial, which is evaluating KRYSTEXXA to improve the management of uncontrolled gout for adults with a kidney transplant, had a total enrollment of 20 patients. Results are expected in the fourth quarter of 2021. In October 2020, the Company announced interim data from the PROTECT trial that were encouraging with respect to the ability of KRYSTEXXA to treat uncontrolled gout in this very sensitive transplant population without compromising kidney function.

Announced Two New KRYSTEXXA Trials to Impact the Patient Experience and Broaden the Patient Population: The Company recently announced it is planning to initiate two new KRYSTEXXA trials in the first half of 2021. The KRYSTEXXA monthly dosing open-label trial is evaluating a monthly dosing regimen of KRYSTEXXA with methotrexate to treat people with uncontrolled gout. The current dosing schedule for KRYSTEXXA is every other week. The KRYSTEXXA retreatment open-label trial is evaluating KRYSTEXXA with methotrexate in patients who have previously failed on KRYSTEXXA. In addition, in October, the Company enrolled the first patient in its open-label shorter infusion duration trial, which is evaluating a shorter infusion duration of KRYSTEXXA with methotrexate. The current infusion time is two hours or longer.

New TEPEZZA Clinical Data Presented at Medical Meetings: New TEPEZZA data were presented at the virtual American Academy of Ophthalmology (AAO) Annual Meeting in November, including data from the OPTIC 48-week follow-up study and OPTIC-X clinical trial that demonstrated a durable response. In addition, case studies of 21 chronic TED patients who showed benefit after treatment with TEPEZZA were presented at the virtual Fall Symposium of the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) in November. This adds to the growing body of evidence supporting the use of TEPEZZA in chronic TED patients, with approximately 30 chronic TED patients across multiple case reports who have consistently demonstrated benefit.

KRYSTEXXA Immunomodulation RECIPE Trial Achieved 86 Percent Response Rate: In November, data were presented from the investigator-initiated RECIPE randomized controlled trial (RCT), evaluating the effect of co-administration of KRYSTEXXA with mycophenolate mofetil (MMF) to increase the complete response rate of KRYSTEXXA, with 86 percent of patients receiving KRYSTEXXA co-administered with MMF achieving the primary endpoint of serum uric acid (sUA) less than or equal to 6 mg/dL at 12 weeks, compared to 40 percent of placebo patients on KRYSTEXXA monotherapy (p-value 0.01). After 12 weeks off of MMF therapy but continuing on KRYSTEXXA therapy, 68 percent of patients achieved a sustained response, compared to 30 percent of placebo patients. The combination was well tolerated with no new safety signals. This trial adds to the growing body of evidence supporting the immunomodulation treatment approach where complete response rates have ranged between 70 and 100 percent.

Established Scholarship Endowments to Foster Equity in Education: In December, the Company announced that it provided $1 million to endow scholarships to be awarded to economically disadvantaged students and students of color at Howard University and in a joint health professionals program at Lake Forest College and Rosalind Franklin University. This adds to the Company’s efforts to combat racism and foster inclusion, which includes a $500,000 donation to community organizations that are addressing racial inequality and racism, as well as internal efforts within the Company to further embed inclusion, diversity, equity and allyship at all levels of the organization.

Received Continued Recognition as a Best Workplace: In 2020, the Company received 13 workplace-related recognitions, including six in the fourth quarter, reflecting the high level of engagement of its employees. Horizon was named to the following lists in the fourth quarter:
Fortune Best Small & Medium Workplaces;
Great Place to Work’s 2020 Best Workplaces for Parents;
National Association for Business Resources’ 2020 Best and Brightest Companies to Work For in the Nation;
Chicago Tribune Top Workplaces 2020;
San Francisco Bay Area’s 2020 Best and Brightest Companies to Work For; and
Dave Thomas Foundation for Adoption Best Adoption-Friendly Workplace list.
Key Research and Development Programs

HZN-825 Diffuse Cutaneous Systemic Sclerosis Program: HZN-825 is an LPAR1 antagonist in development for the treatment of diffuse cutaneous systemic sclerosis (dcSSc), a rare, chronic autoimmune disease marked by fibrosis, or skin thickening, with no FDA-approved treatment options. The Company expects to begin a Phase 2b pivotal trial in the first half of 2021 with the primary endpoint of forced vital capacity after 52 weeks of treatment.

HZN-825 Interstitial Lung Disease Program: As part of its strategy to further explore the potential fibrosis-mediating benefits of LPAR1 antagonism, in mid-2021, the Company expects to begin a Phase 2b pivotal trial with HZN-825 in idiopathic pulmonary fibrosis (IPF), the most common form of interstitial lung disease. IPF is a rare progressive lung disease with a median survival of less than five years with significant unmet need.

TEPEZZA Trial in Chronic TED: The Company expects to initiate a randomized, placebo-controlled trial of TEPEZZA in patients with chronic TED in the second quarter of 2021, assuming normalized supply of TEPEZZA. In chronic TED, the disease is no longer progressive; however, significant disease manifestations such as proptosis (eye bulging) and diplopia (double vision) remain. Although the prescribing information for TEPEZZA includes chronic TED patients, the Company is conducting the trial to generate clinical data to better inform payers and physicians about the use of TEPEZZA in chronic TED.

TEPEZZA Subcutaneous (SC) Administration Program: The Company has initiated a pharmacokinetic trial to explore SC dosing of TEPEZZA, which is currently administered by infusion. The objective of the trial is to inform the potential for additional administration options for TEPEZZA, which could provide greater flexibility for patients and physicians. The TEPEZZA SC administration program includes evaluating Halozyme’s ENHANZE drug delivery technology for a SC formulation of TEPEZZA, with initial early clinical work expected to begin in 2021.

TEPEZZA dcSSc Exploratory Trial: As part of its evaluation of additional potential indications for TEPEZZA, the Company is planning to initiate an exploratory trial in dcSSc by mid-2021, assuming normalized supply of TEPEZZA.

KRYSTEXXA MIRROR Randomized Controlled Trial: The Company is currently evaluating the efficacy and safety of the concomitant use of KRYSTEXXA with methotrexate to increase the complete response rate of KRYSTEXXA in the MIRROR RCT. The primary endpoint of the trial is the proportion of sUA responders (sUA of less than 6 mg/dL) at six months, with secondary endpoints out to 12 months. The registrational trial is designed to enable the submission of results to the FDA to potentially update the prescribing information. The MIRROR RCT follows the MIRROR open-label trial completed in 2019 that demonstrated a 79 percent complete response rate for patients using KRYSTEXXA with methotrexate, nearly double the 42 percent response rate in the KRYSTEXXA Phase 3 clinical program, which evaluated KRYSTEXXA alone. Methotrexate is the immunomodulator most used by rheumatologists and has been shown to reduce anti-drug antibody formation to biologic therapies when used in conjunction with these therapies.

KRYSTEXXA PROTECT Trial in Kidney Transplant Patients with Uncontrolled Gout: In January 2021, the Company completed enrollment of 20 patients in the PROTECT open-label trial, evaluating KRYSTEXXA to improve management of uncontrolled gout for adults with a kidney transplant. Kidney transplant patients have more than a tenfold increase in the prevalence of gout when compared to the general population, and literature suggests that persistently high sUA levels can be associated with organ rejection. Managing uncontrolled gout is one of the most common and significant unmet needs of kidney transplant patients.

KRYSTEXXA Shorter Infusion Duration Trial: In October 2020, the Company enrolled the first patient in its shorter infusion duration trial to evaluate the impact of administering KRYSTEXXA over a significantly shorter infusion duration. Currently, KRYSTEXXA is infused over a two-hour or longer timeframe. A shorter infusion duration administration could meaningfully impact the experience for patients, physicians and sites of care.

KRYSTEXXA Monthly Dosing Trial: The Company is planning to initiate an open-label trial evaluating a monthly dosing regimen of KRYSTEXXA with methotrexate to treat people with uncontrolled gout. The current dosing schedule for KRYSTEXXA is every other week. The goal of the trial is to explore whether a monthly dosing regimen can provide similar outcomes as the current dosing schedule. The trial is expected to initiate in the first half of 2021.

KRYSTEXXA Retreatment Trial: The Company is planning to initiate an open-label trial evaluating KRYSTEXXA with methotrexate in patients who have previously failed KRYSTEXXA. The goal of the trial is to evaluate whether patients can benefit from KRYSTEXXA with methotrexate after developing an immune response to KRYSTEXXA when taken alone. Patients who have previously failed on KRYSTEXXA have limited options available to address their uncontrolled gout. The trial is expected to initiate in the first half of 2021.
Fourth-Quarter Financial Results

Note: For additional detail and reconciliation of non-GAAP financial measures to the most directly comparable GAAP financial measures, please refer to the tables at the end of this release.

Net Sales: Fourth-quarter 2020 net sales were $745.3 million, an increase of 105 percent compared to the fourth quarter of 2019.
Gross Profit: Under U.S. GAAP, the fourth-quarter 2020 gross profit ratio was 78.2 percent compared to 73.9 percent in the fourth quarter of 2019. The non-GAAP gross profit ratio in the fourth quarter of 2020 was 87.1 percent compared to 90.0 percent in the fourth quarter of 2019.
Operating Expenses: Research and development (R&D) expenses were 9.5 percent of net sales and selling, general and administrative (SG&A) expenses were 37.2 percent of net sales. Non-GAAP R&D expenses were 5.2 percent of net sales, and non-GAAP SG&A expenses were 32.3 percent of net sales.
Income Tax Expense: In the fourth quarter of 2020, income tax expense on a GAAP and non-GAAP basis was $39.0 million and $61.6 million, respectively.
Net Income: On a GAAP basis in the fourth quarter of 2020, net income was $190.6 million. Fourth-quarter 2020 non-GAAP net income was $298.5 million.
Adjusted EBITDA: Fourth-quarter 2020 adjusted EBITDA was $371.0 million.
Earnings per Share: On a GAAP basis diluted earnings per share in the fourth quarter of 2020 and 2019 was $0.82 and $2.84, respectively. Non-GAAP diluted earnings per share in the fourth quarter of 2020 and 2019 was $1.28 and $0.56, respectively. Weighted average shares outstanding used for calculating GAAP and non-GAAP diluted earnings per share in the fourth quarter of 2020 were 232.9 million.

Fourth-Quarter Segment Results

Management uses net sales and segment operating income to evaluate the performance of the Company’s two segments, the orphan segment and the inflammation segment. While segment operating income contains certain adjustments to the directly comparable GAAP figures in the Company’s consolidated financial results, it is considered to be prepared in accordance with GAAP for purposes of presenting the Company’s segment operating results.On Oct. 27, 2020, the Company sold its rights to develop and commercialize RAVICTI and BUPHENYL in Japan to Medical Need Europe AB, part of the Immedica Group. The Company has retained the rights to RAVICTI and BUPHENYL in North America.

Fourth-quarter 2020 net sales of the orphan segment, the Company’s strategic growth segment, were $628.2 million, an increase of 151 percent over the prior year’s quarter, driven by the strong performance of TEPEZZA, KRYSTEXXA, PROCYSBI and ACTIMMUNE. The orphan segment represented 84 percent of total fourth-quarter net sales.
Fourth-quarter 2020 orphan segment operating income was $303.0 million, which includes significant investment spend associated with the commercial launch of TEPEZZA.

(1) On Feb. 27, 2020, Dr. Reddy’s Laboratory initiated an at-risk launch of generic VIMOVO in the United States.

(2) In June 2019, the Company divested the rights to MIGERGOT.

Fourth-quarter 2020 net sales of the inflammation segment were $117.1 million, and segment operating income was $66.9 million.
Cash Flow Statement and Balance Sheet Highlights

On a GAAP basis, operating cash flow in the fourth quarter of 2020 was $409.8 million. Non-GAAP operating cash flow was $411.2 million.
As of Dec. 31, 2020, the Company had cash and cash equivalents of $2.080 billion.
As of Dec. 31, 2020, the total principal amount of debt outstanding was $1.018 billion. As of Dec. 31, 2020, the gross-debt-to-last-12-months adjusted EBITDA leverage ratio was 1.0 times, compared to 2.9 times as of Dec. 31, 2019.
2021 Guidance

The Company expects full‐year 2021 net sales to range between $2.70 billion and $2.80 billion, representing 25 percent growth at the midpoint. The Company expects TEPEZZA full-year 2021 net sales of greater than $1.275 billion and KRYSTEXXA full-year 2021 net sales of greater than $500 million. Full-year 2021 adjusted EBITDA is expected to range between $1.14 billion and $1.18 billion, representing 16 percent growth at the midpoint. The Company’s guidance assumes FDA approval of the increased scale drug product manufacturing process of TEPEZZA and the successful completion of future committed manufacturing slots for TEPEZZA and does not reflect the potential impact of the operations of Viela following the close of the acquisition, which is expected to occur by the end of first quarter of 2021, and which would result in an expected reduction of full-year 2021 adjusted EBITDA of approximately $140 million.

Webcast

At 8 a.m. EST / 1 p.m. IST today, the Company will host a live webcast to review its financial and operating results and provide a general business update. The live webcast and a replay may be accessed at View Source Please connect to the Company’s website at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. A replay of the webcast will be available approximately two hours after the live webcast.

Kura Oncology Receives FDA Breakthrough Therapy Designation for Tipifarnib in Head and Neck Squamous Cell Carcinoma

On February 24, 2021 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported that its investigational drug, tipifarnib, has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with recurrent or metastatic HRAS mutant head and neck squamous cell carcinoma (HNSCC) with variant allele frequency ≥ 20% after disease progression on platinum-based chemotherapy (Press release, Kura Oncology, FEB 24, 2021, View Source [SID1234575551]). Tipifarnib is currently being evaluated in an ongoing registration-directed clinical trial (AIM-HN) in this indication of high unmet need.

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HNSCC is the seventh most common cancer worldwide, accounting for more than 885,000 new cases each year. Despite recent treatment advances, prognosis remains poor, with a 5-year survival rate of less than 40%. Second-line treatments provide limited clinical benefit for many patients, with objective response rates (ORR) of 6-16%, median progression-free survival (PFS) of 2-3 months and median overall survival (OS) of 5-8 months.

Tipifarnib’s Breakthrough Therapy Designation is based on data from RUN-HN, a Phase 2 clinical trial evaluating tipifarnib in patients with recurrent or metastatic HRAS mutant HNSCC. Data from this trial, presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Scientific Program in May 2020, showed an ORR of 50%, median PFS of 5.9 months and a median OS of 15.4 months among the 18 evaluable patients. HRAS represents approximately 4-8% of HNSCC patients. The HRAS biomarker can be found on most commercially available genomic panels.

"We are very pleased that the FDA has awarded Breakthrough Therapy Designation to tipifarnib, and we appreciate the agency’s affirmation of its potential to treat this devastating disease," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "We remain focused on conducting our AIM-HN registration-directed trial and look forward to working closely with the FDA to bring this therapy to patients as soon as possible."

The granting of FDA’s Breakthrough Therapy Designation is based on preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over existing therapies. The designation enables expedited development and review of a drug candidate for the treatment of a serious or life-threatening disease. The benefits of a Breakthrough Therapy Designation include the eligibility for priority review, rolling submission of portions of the application and FDA’s organizational commitment involving senior management to provide guidance to the company to help determine the most efficient route to approval.

About Tipifarnib

Tipifarnib, is a potent, selective and orally bioavailable inhibitor of farnesyl transferase in-licensed from Janssen. Previously, tipifarnib was studied in more than 5,000 cancer patients and showed compelling and durable anti-cancer activity in certain patient subsets; however, no molecular mechanism of action had been determined that could explain its clinical activity across a range of solid tumor and hematologic indications. Leveraging advances in next generation sequencing as well as emerging information about cancer genetics and tumor biology, the Company is seeking to identify those patients most likely to benefit from tipifarnib. In addition to Breakthrough Therapy Designation, tipifarnib has been granted Fast Track designation by the FDA for the treatment of patients with HRAS mutant HNSCC. In addition to HNSCC, tipifarnib has demonstrated encouraging clinical activity in a number of additional genetically defined tumor types. Kura has received multiple issued patents for tipifarnib, providing patent exclusivity in the U.S. and foreign countries.

Constellation Pharmaceuticals Announces Fourth-Quarter and Full-Year 2020 Financial Results

On February 24, 2021 Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported its fourth-quarter 2020 financial results and provided a business update (Press release, Constellation Pharmaceuticals, FEB 24, 2021, View Source [SID1234575550]).

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"2020 was an important year for Constellation Pharmaceuticals, marked by several presentations of strong data from our MANIFEST clinical trial for pelabresib (formerly CPI-0610), including our oral presentations at the ASH (Free ASH Whitepaper) Annual Meeting," said Jigar Raythatha, President and Chief Executive Officer of Constellation Pharmaceuticals. "We are executing on our recently launched Phase 3 trial, MANIFEST-2 and believe pelabresib has the potential to transform the standard of care in myelofibrosis. We also continue to advance our pipeline of product candidates with CPI-0209 and the newly announced CPI-482."

Pelabresib (CPI-0610)

Constellation presented an update of MANIFEST data in two oral presentations and three posters at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2020 Annual Meeting, which are available on Constellation’s website.
CPI-0209

Patients continue to be advanced through multiple dosing cohorts in the Phase 1 dose escalation portion of a Phase 1/2 clinical trial of the EZH2 inhibitor CPI-0209.
Data from the Phase 1 portion will guide our recommended Phase 2 dose (RP2D) selection for expansion arms in select tumor types.
Clinical data will be supplemented with data on biomarkers to identify patients most likely to benefit.
CPI-482

The Company named CPI-482 as a new development candidate, targeting LSD1. CPI-482 reinforces our commitment to addressing unmet needs in hematologic diseases, particularly myeloproliferative neoplasms (MPNs). Furthermore, our development strategy with CPI-482 will leverage our unique translational research and understanding of epigenetic mechanisms in myeloid cells.
2020 Leadership Updates

Constellation strengthened its senior management team with the appointment of Brendan Delaney as Chief Commercial Officer, effective January 2021. Previously, Mr. Delaney served as Chief Commercial Officer of Immunomedics and Vice President, U.S. Commercial Hematology Oncology at Celgene. Mr. Delaney will build and lead the Company’s commercial organization and pre-launch preparations in support of pelabresib.
Earlier in the year, Constellation appointed Jeffrey Humphrey, M.D. as Chief Medical Officer. Previously, Dr. Humphrey served as Chief Development Officer at Kyowa Kirin Co., where he oversaw the development of over twenty drug candidates including regulatory submissions leading to three drug approvals in the United States and Europe.
2021 Milestones

The Company anticipates achieving the following milestones during 2021:

Pelabresib – Provide MANIFEST translational data update mid-year

Pelabresib – Provide MANIFEST clinical data update and update on new indications by end of year

CPI-0209 – Provide Phase 1 data update by mid-year

CPI-0209 – Provide update on monotherapy cohorts from Phase 2 by end of year

Fourth Quarter 2020 Financial Results

Cash, cash equivalents, and marketable securities as of December 31, 2020, were $421.4 million. 
Research and development (R&D) expenses increased 47.2% year over year to $27.4 million in the fourth quarter of 2020, mainly due to increased clinical trial expenses.
General and administrative (G&A) expenses grew 56.2% year over year to $8.5 million in the fourth quarter of 2020, primarily due to building out the organization of the company.
The net loss attributed to common shareholders increased 54.4% year over year to $37.4 million for the fourth quarter of 2020, mainly due to increased R&D and G&A expenses. The net loss per share attributable to common shareholders increased by 14.5% to $0.79 per share, due to an increase in net loss and partly off-set by an increase in weighted shares outstanding.
Full Year 2020 Financial Results

Research and development (R&D) expenses increased 43.7% year over year to $95.5 million for full-year 2020, mainly due to increased clinical trial expenses.
General and administrative (G&A) expenses grew 49.8% year over year to $29.3 million for full-year 2020, primarily due to building out the organization of the company.
The net loss attributed to common shareholders increased 47.7% year over year to $126.4 million for full-year 2020, mainly due to increased R&D and G&A expenses. The net loss per share attributable to common shareholders decreased 7.6% to $2.81 per share, largely due to an increase in weighted average shares outstanding as a result of the additional shares issued in June 2020.
Financial Guidance

Constellation expects that its current cash, cash equivalents, and marketable securities balance will fund operations into mid-2023.

About MANIFEST-2

MANIFEST-2 is a global, blinded, randomized Phase 3 clinical study with pelabresib in combination with ruxolitinib versus placebo plus ruxolitinib in JAK-inhibitor-naïve patients with primary myelofibrosis or post-ET or post-PV myelofibrosis who have splenomegaly and symptoms requiring therapy. It is designed to enroll approximately 310 patients, randomized 1:1 to the pelabresib + ruxolitinib arm or the placebo + ruxolitinib arm. The primary endpoint of the study is a ≥35% reduction in spleen volume (SVR35) from baseline at 24 weeks. A key secondary endpoint of the study is 50% or greater improvement in Total Symptom Score (TSS50) from baseline at 24 weeks. Other endpoints include bone marrow fibrosis grade improvements, duration of transfusion independence, rate of red-blood-cell transfusion for the first 24 weeks, and hemoglobin response.

About MANIFEST

MANIFEST is an open-label Phase 2 clinical trial of pelabresib in patients with myelofibrosis (MF), a rare cancer of the bone marrow that disrupts the body’s normal production of blood cells. Constellation is evaluating CPI-0610 in combination with ruxolitinib in JAK-inhibitor-naïve MF patients (Arm 3), with a primary endpoint of the proportion of patients with a ≥35% spleen volume reduction from baseline (SVR35) after 24 weeks of treatment. Constellation is also evaluating CPI-0610, either as a monotherapy in patients who are resistant to, intolerant of, or ineligible for ruxolitinib and no longer on the drug (Arm 1), or as add-on therapy in combination with ruxolitinib in patients with a sub-optimal response to ruxolitinib or MF progression (Arm 2). Patients in Arms 1 and 2 are being stratified based on TD status. The primary endpoint for the patients in cohorts 1A and 2A, who were TD at baseline, is conversion to TI for 12 consecutive weeks. The primary endpoint for the patients in cohorts 1B and 2B, who were not TD at baseline, is the proportion of patients with a ≥35% spleen volume reduction from baseline after 24 weeks of treatment.

Syndax Announces Participation at Two Upcoming Investor Conferences

On February 24, 2021 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that members of its management team will participate in two upcoming virtual investor conferences (Press release, Syndax, FEB 24, 2021, View Source [SID1234575549]):

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A panel at the Cowen 41st Annual Health Care Conference at 11:40 a.m. ET on Wednesday, March 3, 2021.

A fireside chat at the Barclays Global Healthcare Conference at 3:35 p.m. ET on Tuesday, March 9, 2021.
A live webcast of the Barclays presentation can be accessed from the Investor section of the Company’s website at www.syndax.com, where a replay of the event will also be available for a limited time.