On March 25, 2021 CymaBay Therapeutics, Inc. (NASDAQ: CBAY), a clinical-stage biopharmaceutical company focused on developing therapies for liver and other chronic diseases with high unmet need, reported corporate updates and financial results for the fourth quarter and fiscal year ended December 31, 2020 (Press release, CymaBay Therapeutics, MAR 25, 2021, View Source [SID1234577144]).

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In the fourth quarter of 2020 and through early March 2021, CymaBay made significant progress reinitiating the development program for seladelpar in primary biliary cholangitis (PBC). With multiple clinical sites activated, patient recruitment is underway in RESPONSE, a global Phase 3 registrational study evaluating seladelpar in patients with PBC. In addition, we have also initiated ASSURE, an open-label, long-term study of seladelpar in patients with PBC intended to collect additional safety data to support registration.

Sujal Shah, President and CEO of CymaBay, stated, "One year ago today, our work towards finding novel treatments for patients with chronic, inflammatory and metabolic diseases was on hold as we completed the important work of ensuring patient safety before moving forward. Today we have four active clinical studies ongoing across three programs. We continue to make great progress towards restarting our seladelpar development program with RESPONSE as we execute on a focused strategy to complete late-stage development of seladelpar for patients with PBC. Results from our previous Phase 3 study in PBC, ENHANCE, presented at The Liver Meeting 2020, highlighted the anti-cholestatic, anti-inflammatory and anti-pruritic effects of seladelpar in patients with PBC that we believe support the potential for seladelpar to address key unmet needs for patients suffering from this disease. In addition to our core focus in PBC, we continue to evaluate seladelpar for other indications and are excited about our early-stage pipeline maturing in the coming months."

Recent Corporate Highlights

Initiated RESPONSE, a 52-week, placebo-controlled, randomized, global, Phase 3 registrational study evaluating the safety and efficacy of seladelpar in patients with PBC. This study will target enrolling 180 patients, who have an inadequate response to, or intolerance to, ursodeoxycholic acid, in a 2:1 randomization to oral, once daily seladelpar 10 mg or placebo. The primary outcome measure is the responder rate at 52 weeks. A responder is defined as a patient who achieves an alkaline phosphatase level < 1.67 times the upper limit of normal with at least a 15% decrease from baseline and has a normal level of total bilirubin. Additional key outcomes of efficacy will compare the rate of normalization of alkaline phosphatase at 52 weeks and the level of pruritus at 6-months for patients with moderate to severe pruritus at baseline assessed by a numerical rating scale recorded with an electronic diary.

Initiated ASSURE, an open-label, long-term study of seladelpar in patients with PBC intended to collect additional long-term safety data to support registration. The first subjects will consist of patients who have participated in CymaBay’s prior studies of seladelpar in PBC, including the patients who completed the open-label Phase 2 study and enrolled into the previous long-term study and ENHANCE. Patients who complete RESPONSE, and potentially other future PBC studies with seladelpar, will also have the opportunity to enroll in ASSURE.

Presented results from two separate studies of seladelpar in patients with PBC and NASH at The Liver Meeting 2020 as follows:

Oral, late-breaking presentation by Professor Gideon Hirschfield, MD, on November 16 highlighting results from ENHANCE, a Phase 3 study of seladelpar in patients with PBC
"Poster of Distinction" presentation by Dr. Stephen Harrison, MD, featuring results from a Phase 2 paired-liver biopsy study of seladelpar in patients with NASH

In November 2020, we announced a Phase 2a proof-of-pharmacology study to evaluate the potential for MBX-2982, a GPR119 agonist, to prevent hypoglycemia in patients with type 1 diabetes (T1D). The study is being conducted by the AdventHealth Translational Research Institute (TRI) in Orlando, Florida and fully funded by The Leona M. and Harry B. Helmsley Charitable Trust with CymaBay retaining full rights to MBX-2982. TRI commenced startup activities in early 2021 and topline results are currently anticipated in late 2021.

Initiated a single and multiple ascending dose study of CB-0406 in healthy subjects to establish its pharmacokinetics, safety and maximum tolerated dose. CB-0406 is a non-agonist ligand of PPARγ that attenuates the expression of inflammatory genes.

Held $146.3 million in cash, cash equivalents and short-term investments on December 31, 2020. We believe that cash and investments are sufficient to fund CymaBay’s current operating plan into mid-2022.

Due to the ongoing effects of the global coronavirus pandemic, CymaBay continues to conduct its operations remotely for all employees, which has allowed business activities to continue as seamlessly as possible. CymaBay continues to closely monitor pandemic developments and their associated risks to the business, including the restarting of its clinical development of seladelpar, and will continue to take actions available to mitigate them where possible. Further, all CymaBay’s actions will continue to be guided by a commitment to ensuring the health and safety of its employees as well as patients enrolled in its clinical studies.
Fourth Quarter and Year Ended December 31, 2020 Financial Results

Research and development expenses for the three and twelve months ended December 31, 2020 were $10.7 million and $35.9 million, respectively. This compared to R&D expenses of $20.9 million and $83.8 million for the three and twelve months ended December 31, 2019, respectively. Research and development expenses in the three and twelve months ended December 31, 2020 were lower than the corresponding periods in 2019 primarily due to a decline in clinical trial activities related to the termination of our Phase 3 PBC, Phase 2b NASH, and Phase 2 PSC clinical trials, and other studies, after the seladelpar development program was placed on hold from November 2019 through July 2020. Clinical development of seladelpar in PBC was resumed in late 2020, and these clinical expense reductions were offset in part by increases in clinical trial costs associated with the commencement of RESPONSE and ASSURE, our two new global late-stage clinical trials in PBC.

General and administrative expenses for the three and twelve months ended December 31, 2020 were $5.2 million and $17.4 million, respectively. This compared to $4.5 million and $19.2 million for the three and twelve months ended December 31, 2019, respectively. General and administrative expenses in the year 2020 were lower than in 2019 due to lower employee compensation costs following the completion of a reduction-in-force plan in late 2019. General and administrative expenses in the three months ended December 31, 2020 were higher than the corresponding period in 2019 due to higher employee compensation associated with the hiring of additional personnel upon resumption of development of seladelpar in the second half of 2020.

Net loss for the three and twelve months ended December 31, 2020 was $15.8 million, or ($0.23) per diluted share, and $51.0 million, or ($0.74) per diluted share, respectively. This compared to net loss of $29.4 million, or ($0.43) per diluted share, and $102.8 million, or ($1.53) per diluted share, in the three and twelve months ended December 31, 2019, respectively. Net loss was lower largely due to decreases in clinical operating expenses which resulted from the temporary clinical hold placed on the seladelpar development program. With development of seladelpar restarted during the second half of 2020, we expect our operating expenses to increase in 2021 as we continue to execute on our clinical development plans.
Conference Call Details

CymaBay will host a conference call today at 4:30 p.m. ET to discuss fourth quarter and fiscal year end 2020 financial results and provide a business update. To access the live conference call, please dial 877-407-0784 from the U.S. and Canada, or 201-689-8560 internationally, Conference ID# 13715944. To access the live and subsequently archived webcast of the conference call, go to the Investors section of the company’s website at View Source

On March 25, 2021 Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, reported that Shehnaaz Suliman, M.D., MBA, M.Phil., president and chief operating officer of Alector, will participate in a fireside chat at Stifel’s 3rd Annual CNS Day on Thursday, April 1, 2021, at 9:30 a.m. ET (Press release, Alector, MAR 25, 2021, View Source [SID1234577143]).

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A live webcast of the fireside chat will be available on the "Events & Presentations" page within the Investors section of the Alector website at View Source A replay will be available on the Alector website for 30 days following the event.

On March 25, 2021 Nkarta, Inc. (Nasdaq: NKTX), a clinical-stage biopharmaceutical company developing engineered natural killer (NK) cell therapies to treat cancer, reported financial results for the fourth quarter and year ended December 31, 2020 (Press release, Nkarta, MAR 25, 2021, View Source [SID1234577142]).

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"We continue our work to supercharge the distinctive tumor-killing power of healthy donor-derived natural killer cells and advance our co-lead development programs in allogeneic, off-the-shelf, engineered cell therapy," said Paul J. Hastings, President and Chief Executive Officer of Nkarta. "Our goal remains to report early clinical data from the dose finding portion of our ongoing clinical trial of NKX101 by the end of this year. In addition, we are on track to file the IND application for NKX019 this month and begin patient dosing in a multi-center clinical trial for patients with B cell malignancies in the second half of 2021. Nkarta remains committed to the transformative potential of CAR NK cell therapy for cancer patients and we strive to keep patients at the center of all that we do."

Anticipated Clinical Milestones

In the first quarter of 2021, Nkarta plans to file an Investigational New Drug (IND) application for NKX019, a CAR (chimeric antigen receptor) NK cell therapy candidate engineered to target tumors expressing CD19 antigen for the treatment of B-cell malignancies. Following the regulatory clearance of the IND, Nkarta expects patient dosing in a Phase 1 clinical trial of NKX019 to initiate in the second half of 2021.
Nkarta expects to manufacture NKX019 clinical supply for the Phase 1 clinical trial at its in-house cGMP clinical manufacturing facility located in South San Francisco, California.
Nkarta aims to present initial clinical data from its ongoing clinical trial of NKX101 in patients with r/r AML and MDS by year end. In the Phase 1 study, patients receive multiple doses of NKX101 during a 28-day treatment cycle and are eligible to receive a second cycle of treatment upon evidence of tolerability and disease response.
2022 milestones are expected to include an IND amendment for NKX101 for the treatment of solid tumors and an IND application for Nkarta’s third engineered CAR NK cell product candidate that is designed to target solid tumors and hematologic malignancies.
Fourth Quarter and Full Year 2020 Financial Highlights

Cash and Cash Equivalents: As of December 31, 2020, Nkarta had cash, cash equivalents, restricted cash and short-term investments of $315.3 million, which includes proceeds from the Company’s July 2020 IPO of $265.1 million, net of underwriting discounts and commissions and other offering costs.

R&D Expenses: Research and development expenses were $36.2 million for the full year 2020 and $11.3 million for the fourth quarter of 2020. Non-cash stock-based compensation expense included in R&D expense was $1.9 million for the full year 2020 and $0.8 million for the fourth quarter of 2020.

G&A Expenses: General and administrative expenses were $15.3 million for the full year 2020 and $6.7 million for the fourth quarter of 2020. Non-cash stock-based compensation expense included in G&A expense was $4.9 million for the full year 2020 and $3.3 million for the fourth quarter of 2020.

Net Loss. Net loss was $91.4 million, or $5.44 per basic and diluted share, for the full year 2020. This net loss includes a non-recurring $40.2 million non-cash change in fair value of preferred stock purchase liability. Net loss was $17.9 million, or $0.55 per basic and diluted share, for the quarter ended December 31, 2020.
Financial Guidance

Nkarta expects its current cash and cash equivalents will be sufficient to fund its current operating plan into at least the second half of 2023.
About NKX101
NKX101 is an investigational, off-the-shelf cancer immunotherapy that uses natural killer (NK) cells derived from the peripheral blood of healthy donors and engineered with membrane-bound IL15 and a chimeric antigen receptor (CAR) targeting NKG2D ligands on tumor cells. NKG2D, a key activating receptor found on naturally occurring NK cells, induces a cell-killing immune response through the detection of stress ligands that are widely expressed on cancer cells. By engineering NKX101 with the proprietary NKG2D-based CAR, the ability of NK cells to recognize and kill tumor cells in pre-clinical models is increased significantly compared to non-engineered NK cells. The addition of membrane-bound IL15, a proprietary version of a cytokine for activating NK cell growth, has been shown in pre-clinical models to enhance the proliferation, persistence and sustained activity of NK cells. A multi-center Phase 1 clinical trial of NKX101 in patients with relapsed/refractory acute myeloid leukemia (AML) or higher risk myelodysplastic syndromes (MDS) is currently enrolling. Additional information about the clinical trial is available on ClinicalTrials.gov, identifier NCT04623944.

About NKX019
NKX019 is an investigational, off-the-shelf cancer immunotherapy that uses natural killer (NK) cells derived from the peripheral blood of healthy donors and engineered with a chimeric antigen receptor (CAR) targeting the CD19 antigen and membrane-bound IL15. CD19 antigen is a B-cell marker and validated target for B-cell cancer therapies. NKX019 uses the CAR to target and bind to CD19, leading to an immune response that eliminates CD19-expressing cells in preclinical studies. The addition of membrane-bound IL15, a proprietary version of a cytokine for activating NK cell growth, has been shown in preclinical models to enhance the proliferation, persistence and activity of NK cells. Nkarta plans to file an IND application with the FDA in the first quarter of 2021. Initiation of a Phase 1 clinical trial of NKX019 in patients with advanced relapsed/refractory B cell malignancies is planned for the second half of 2021.

About Nkarta’s Platform and Natural Starting Materials
Nkarta’s engineering platform utilizes healthy adult donors as the source for NK cells. By enlisting this natural source of NK cells, Nkarta starts with bona fide NK cells already endowed with inherent tumor-recognizing and cytotoxic potencies, as compared to other more complex cell sources where these basic therapeutic features must be painstakingly designed and synthetically added to the cells. Healthy donor-derived NK cells are also available in abundance, providing a large quantity of cells with which to begin the efficient two-week manufacturing process. Finally, healthy donor-derived adult cells consist of a diverse repertoire of NK cells. By utilizing a cell source that contains the broad and naturally occurring gamut of NK cells, Nkarta has the potential to capitalize on the inherent diversity of the innate immune system and select for different NK cell sub-populations with desired characteristics.

About Nkarta’s NK Cell Technologies
Nkarta has pioneered a novel discovery and development platform for the engineering and efficient production of allogeneic, off-the-shelf natural killer (NK) cell therapy candidates. The approach harnesses the innate ability of NK cells to recognize and kill tumor cells. To enhance the inherent biological activity of NK cells, Nkarta genetically engineers the cells with a targeting receptor designed to recognize and bind to specific proteins on the surface of cancerous cells. This receptor is fused to co-stimulatory and signaling domains to amplify cell signaling and NK cell cytotoxicity. Upon binding the target, NK cells become activated and release cytokines that enhance the immune response and cytotoxic granules that lead to killing of the target cell. All of Nkarta’s NK current cell therapy candidates are also engineered with a membrane-bound IL15, a proprietary version of a cytokine known for activating NK cell growth, to enhance the persistence and activity of the NK cells.

Nkarta’s manufacturing process generates an abundant supply of NK cells that, at commercial scale, is expected to be significantly lower in cost than other current allogeneic and autologous cell therapies. Key to this efficiency is the rapid expansion of donor-derived NK cells using a proprietary NKSTIM cell line, leading to the production of hundreds of individual doses from a single manufacturing run. The platform also features the ability to freeze and store CAR NK cells for an extended period of time and is designed to enable immediate, off-the-shelf administration to patients at the point of care.

On March 25, 2021 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism to treat genetically defined diseases, reported that its shareholders voted to approve the previously disclosed sale of its commercial, clinical and research-stage oncology portfolio to Servier Pharmaceuticals, LLC, an independent global pharmaceutical company (Press release, Agios Pharmaceuticals, MAR 25, 2021, View Source [SID1234577141]).

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Approximately 99.9% of the shares voted at the Special Meeting, representing approximately 90% of the outstanding shares entitled to vote, were voted in favor of the transaction. Agios will file the final vote results, as certified by the independent Inspector of Election, on a Form 8-K with the U.S. Securities and Exchange Commission.

Agios expects the close of the transaction to occur around March 31, 2021, subject to the satisfaction of customary closing conditions.

Agios also announced that its board of directors authorized the repurchase of up to $1.2 billion of its outstanding shares after the close of the transaction. Agios expects to conduct the share repurchases over the next 12-18 months, including executing a meaningful portion of the planned repurchases by year-end through a combination of 10b5-1 plans, open market purchases and potentially privately negotiated block sales.

On March 25, 2021 Neurocrine Biosciences, Inc. (Nasdaq: NBIX) reported that it will present at the Stifel 3rd Annual CNS Day at 12:30 p.m. Eastern Time on Thursday Apr. 1, 2021 (Press release, Neurocrine Biosciences, MAR 25, 2021, View Source [SID1234577140]). Eiry Roberts, Chief Medical Officer, and Kyle Gano, Chief Business Development and Strategy Officer, will present at the conference.

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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

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The live presentation will be webcast and may be accessed on the Company’s website under Investors at www.neurocrine.com. A replay of the presentation will be available on the website approximately one hour after the conclusion of the events and will be archived for approximately one month.