On February 28, 2022 Heron Therapeutics, Inc. (Nasdaq: HRTX), a commercial-stage biotechnology company focused on improving the lives of patients by developing best-in-class treatments to address some of the most important unmet patient needs, reported financial results for the three and twelve months ended December 31, 2021 and highlighted recent corporate updates (Press release, Heron Therapeutics, FEB 28, 2022, View Source [SID1234609128]).

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Recent Corporate Updates

Acute Care Franchise

ZYNRELEF:

The ZYNRELEF (bupivacaine and meloxicam) extended-release solution New Drug Application (NDA) was approved by the U.S. Food and Drug Administration (FDA) in May 2021. In December 2021, the FDA approved our supplemental New Drug Application (sNDA) for ZYNRELEF, which significantly expanded the indication statement, now covering approximately 7 million procedures annually. ZYNRELEF is currently indicated for use in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after foot and ankle, small-to-medium open abdominal, and lower extremity total joint arthroplasty surgical procedures. The FDA also agreed to Heron’s proposal for a second sNDA, planned for later this year, designed to further expand the indication statement.

ZYNRELEF became commercially available in the U.S. on July 1, 2021, and net product sales for the three and twelve months ended December 31, 2021 were $0.8 million and $2.9 million, respectively.

During the first two quarters of commercial launch ended December 31, 2021, over 300 unique accounts purchased ZYNRELEF with 70% of those accounts reordering the product. ZYNRELEF end-user (hospitals and ambulatory surgical centers (ASC)) demand units’ volume sales increased by 126% in the fourth quarter over the prior quarter.

As of February 25, 2022, ZYNRELEF has received 260 formulary approvals, with over a 90% hospital approval rate, and over 60% of formulary approvals have been for unrestricted use. Over 100 additional formulary review meetings are scheduled through March 31, 2022.

Multiple commercial and Medicaid payers covering over 120 million lives have agreed to reimburse ZYNRELEF outside of the surgical bundle payment for surgeries performed in ASCs, with many of these covered lives also having their hospital outpatient procedures reimbursed outside the surgical bundle payment. Commercial and Medicaid payers represent more than 80% of our target patients in the outpatient setting. On November 2, 2021, we were issued a specific C-code (C9088) for separate reimbursement in the ASC setting of care effective January 1, 2022.

In the fourth quarter of 2021, Heron received FDA approval of two manufacturing supplements to the NDA for ZYNRELEF to add a large-scale secondary supplier of our proprietary polymer and to add larger-scale manufacturing of ZYNRELEF. These approvals will allow for the manufacturing of millions of doses of ZYNRELEF annually at a significantly reduced cost of products sales.

NDA Submission for HTX-019 for Prevention of PONV in Adults Under Review: A 505(b)(2) NDA for HTX-019 for the prevention of postoperative nausea and vomiting (PONV) in adults was submitted to the FDA in November 2021. The FDA accepted the NDA for filing and set a Prescription Drug User Fee Act (PDUFA) goal date of September 17, 2022.
Oncology Care Franchise

2021 Oncology Care Franchise Net Product Sales: For the three and twelve months ended December 31, 2021, oncology care franchise net product sales were $19.9 million and $83.4 million, respectively, compared to $20.6 million and $88.6 million, respectively, for the same periods in 2020. During 2021, Heron’s oncology care franchise net product sales have stabilized with moderate growth expected in 2022.
CINVANTI

Net Product Sales: Net product sales of CINVANTI (aprepitant) injectable emulsion for the three and twelve months ended December 31, 2021 were $17.4 million and $73.5 million, respectively, compared to $20.3 million and $87.8 million, respectively, for the same periods in 2020.

In the fourth quarter of 2021, Heron received FDA approval of a manufacturing supplement to the NDA for CINVANTI to add larger-scale manufacturing of CINVANTI. This approval will significantly reduce the cost of products sales.
SUSTOL

Net Product Sales: Net product sales of SUSTOL (granisetron) extended-release injection for the three and twelve months ended December 31, 2021 were $2.5 million and $9.9 million, respectively, compared to $0.3 million and $0.8 million, respectively, for the same periods in 2020.

2022 Oncology Care Franchise Net Product Sales Guidance: Heron currently expects the first quarter of 2022 net product sales for the oncology care franchise in the range of $20 million to $22 million. The Company is not providing full-year 2022 financial guidance at this time due to the uncertainty around the COVID-19 pandemic and its impact on patient care.
"2021 was a tremendous year for Heron. The approval and successful commercial launch of ZYNRELEF was a game-changing milestone for patients, healthcare providers, and pain management. We are extremely pleased with the very positive feedback from patients and surgeons about the benefits of ZYNRELEF, which has resulted in a high reorder rate. With our new broader label for ZYNRELEF and the recent rapid decline of COVID, we expect to significantly expand ZYNRELEF’s commercial footprint this year," said Barry Quart, Pharm.D., Chairman and Chief Executive Officer of Heron. "In oncology care, our CINV portfolio has stabilized and is poised for sales growth in 2022."

Financial Results

Net product sales for the three and twelve months ended December 31, 2021 were $20.7 million and $86.3 million, respectively, compared to $20.6 million and $88.6 million, respectively, for the same periods in 2020.

Heron’s net loss for the three and twelve months ended December 31, 2021 was $54.6 million and $220.7 million, or $0.54 per share and $2.24 per share, respectively, compared to $62.3 million and $227.3 million, or $0.68 per share and $2.50 per share, respectively, for the same periods in 2020. Net loss for the three and twelve months ended December 31, 2021 included non-cash, stock-based compensation expense of $12.9 million and $46.9 million, respectively, compared to $16.0 million and $50.2 million, respectively, for the same periods in 2020.

As of December 31, 2021, Heron had cash, cash equivalents and short-term investments of $157.6 million, compared to $208.5 million as of December 31, 2020. Net cash used for operating activities for the year ended December 31, 2021 was $203.4 million, compared to $184.8 million for the same period in 2020. The increase in our net cash used for operating activities was primarily due to changes in working capital related to the launch of ZYNRELEF in July 2021, including manufacturing of commercial inventory. We expect net cash used for operating activities of $44 million to $48 million in the first quarter of 2022. We anticipate that our net cash usage will continue to moderate lower throughout 2022 as net product sales increase and we realize cost savings from anticipated larger-scale manufacturing.

Conference Call and Webcast

Heron will host a conference call and webcast on February 28, 2022 at 4:30 p.m. ET. The conference call can be accessed by dialing 877-311-5906 for domestic callers and 281-241-6150 for international callers. Please provide the operator with the passcode 9276143 to join the conference call. The conference call will also be available via webcast under the Investor Relations section of Heron’s website at www.herontx.com. An archive of the teleconference and webcast will also be made available on Heron’s website for 60 days following the call.

About ZYNRELEF for Postoperative Pain

ZYNRELEF is the first and only dual-acting local anesthetic that delivers a fixed-dose combination of the local anesthetic bupivacaine and a low dose of nonsteroidal anti-inflammatory drug meloxicam. ZYNRELEF is the first modified-release local anesthetic to be classified by the FDA as an "extended-release" product because ZYNRELEF is also the first and only extended-release local anesthetic to demonstrate in Phase 3 studies significantly reduced pain and significantly increased proportion of patients requiring no opioids through the first 72 hours following surgery compared to bupivacaine solution, the current standard-of-care local anesthetic for postoperative pain control. ZYNRELEF was initially approved by the FDA in May 2021 for use in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after bunionectomy, open inguinal herniorrhaphy and total knee arthroplasty. In December 2021, the FDA approved an expansion of ZYNRELEF’s indication. ZYNRELEF is now indicated in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after foot and ankle, small-to-medium open abdominal, and lower extremity total joint arthroplasty surgical procedures. Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large multilevel spinal, and head and neck procedures. In September 2020, the European Commission granted a marketing authorization for ZYNRELEF for the treatment of somatic postoperative pain from small- to medium-sized surgical wounds in adults. As of January 1, 2021, ZYNRELEF is approved in 31 European countries including the countries of the European Union and European Economic Area and the United Kingdom.

Please see full prescribing information, including Boxed Warning, at www.ZYNRELEF.com.

About HTX-019 for PONV

HTX-019 is an IV injectable emulsion formulation designed to directly deliver aprepitant, the active ingredient in EMEND (aprepitant) capsules, which is the only substance P/neurokinin-1 (NK1) receptor antagonist (RA) to be approved in the U.S. for the prevention of PONV in adults. The FDA-approved dose of oral EMEND is 40 mg for PONV prevention, which is given within 3 hours prior to induction of anesthesia for surgery. In a Phase 1 clinical trial, 32 mg of HTX-019 as a 30-second IV injection was demonstrated to be bioequivalent to oral aprepitant 40 mg. The NDA for HTX-019 for PONV was submitted in November 2021 and the FDA set a PDUFA goal date of September 17, 2022.

About CINVANTI for Chemotherapy Induced Nausea and Vomiting (CINV) Prevention

CINVANTI, in combination with other antiemetic agents, is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin as a single-dose regimen, delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) as a single-dose regimen, and nausea and vomiting associated with initial and repeat courses of MEC as a 3-day regimen. CINVANTI is an IV formulation of aprepitant, an NK1 RA. CINVANTI is the first IV formulation to directly deliver aprepitant, the active ingredient in EMEND capsules. Aprepitant (including its prodrug, fosaprepitant) is the only single-agent NK1 RA to significantly reduce nausea and vomiting in both the acute phase (0–24 hours after chemotherapy) and the delayed phase (24–120 hours after chemotherapy). The FDA-approved dosing administration included in the U.S. prescribing information for CINVANTI include 100 mg or 130 mg administered as a 30-minute IV infusion or a 2-minute IV injection.

Please see full prescribing information at www.CINVANTI.com.

About SUSTOL for CINV Prevention

SUSTOL is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. SUSTOL is an extended-release, injectable 5-hydroxytryptamine type 3 RA that utilizes Heron’s Biochronomer drug delivery technology to maintain therapeutic levels of granisetron for ≥5 days. The SUSTOL global Phase 3 development program was comprised of two, large, guideline-based clinical studies that evaluated SUSTOL’s efficacy and safety in more than 2,000 patients with cancer. SUSTOL’s efficacy in preventing nausea and vomiting was evaluated in both the acute phase (0–24 hours after chemotherapy) and delayed phase (24–120 hours after chemotherapy).

On February 28, 2022 Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) reported financial results for the three months and full-year ended December 31, 2021 and provided an update on key milestones (Press release, Lexicon Pharmaceuticals, FEB 28, 2022, View Source [SID1234609127]).

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"We remain focused on advancing sotagliflozin for the millions of people suffering from heart failure and living with type 2 diabetes on a daily basis. We announced today that we voluntarily withdrew the sotagliflozin NDA to correct a technical issue that we recently identified, and we plan to promptly resubmit early in the second quarter of 2022," said Lonnel Coats, Lexicon’s chief executive officer. "In addition, we are looking forward to completing and announcing top-line results in the coming months from our two proof-of-concept Phase 2 studies of LX9211 in diabetic peripheral neuropathic pain and post-herpetic neuralgia."

Fourth Quarter Highlights

Sotagliflozin

Lexicon submitted a New Drug Application (NDA) to the FDA at the end of the fourth quarter of 2021 seeking approval for the marketing and sale of sotagliflozin, to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent visits for heart failure in adult patients with type 2 diabetes with either worsening heart failure or additional risk factors for heart failure irrespective of left ventricular ejection fraction. Today, Lexicon announced its voluntary withdrawal and planned near-term resubmission of the NDA to correct a technical issue with the submission recently identified by the company.
A new analysis evaluating the clinical benefit of sotagliflozin in heart failure and blood glucose control across the full range of kidney function was presented at the American Heart Association Scientific Sessions 2021. Sotagliflozin significantly reduced total cardiovascular deaths, hospitalizations for heart failure, and urgent visits for heart failure, as well as decreased hemoglobin A1c, across the full range of kidney function studied, including individuals with moderate-to-severe chronic kidney disease.
LX9211

Patient enrollment continued in two ongoing Phase 2 clinical studies of LX9211: RELIEF-DPN-1 for the treatment of diabetic peripheral neuropathic pain and RELIEF-PHN-1 for the treatment of post-herpetic neuralgia. Lexicon anticipates completing recruitment this week for RELIEF-DPN-1 and expects top-line results for the study by the end of the second quarter of 2022. Top-line results for RELIEF-PHN-1 are expected in the third quarter of 2022.
Fourth Quarter and Full-Year 2021 Financial Highlights

Unless otherwise stated, all comparisons are for the fourth quarter and full year of 2021 compared to the fourth quarter and full year of 2020.

Revenues: Revenues were negligible for the fourth quarters of 2021 and 2020. Full-year revenues were negligible in 2021 as compared to $24.0 million for 2020, primarily due to the absence of product revenues in 2021 as a result of Lexicon’s sale of its XERMELO product and related assets to TerSera Therapeutics LLC during the third quarter of 2020.

Research and Development (R&D) Expenses: R&D expenses for the fourth quarter of 2021 increased to $16.5 million from $1.0 million for the corresponding period in 2020. The R&D expense in the fourth quarter of 2020 reflected a reduction in external clinical development cost estimates primarily related to sotagliflozin R&D expenses. Full-year R&D expenses decreased to $55.0 million in 2021 from $153.6 million in 2020, primarily due to lower sotagliflozin clinical external research expenses, partially offset by higher LX9211 clinical external research expenses.

Selling, General and Administrative (SG&A) Expenses: SG&A expenses for the fourth quarter of 2021 increased to $8.8 million from $6.4 million for the corresponding period in 2020, primarily due to higher legal fees during the quarter. Full-year SG&A expenses for 2021 decreased to $32.3 million from $47.2 million, primarily due to lower salaries and benefits and marketing costs.

Gain on Sale of XERMELO: A gain of $132.6 million was recognized during 2020 from the sale of XERMELO and related assets to TerSera in September 2020.

Net Income (Loss): Net loss for the fourth quarter of 2021 was $25.6 million, or $0.17 per share, as compared to a net loss of $5.5 million, or $0.04 per share, in the corresponding period in 2020. For the fourth quarter of 2021 and 2020, net loss included non-cash, stock-based compensation expense of $2.2 million and $2.7 million, respectively. Net loss for the full-year was $87.8 million, or $0.60 per share, in 2021 as compared to a net loss of $58.6 million, or $0.53 per share, in 2020. For the full years of 2021 and 2020, net loss included non-cash, stock-based compensation expense of $10.6 million and $13.3 million, respectively.

Cash and Investments: As of December 31, 2021, Lexicon had $86.7 million in cash and investments, as compared to $152.3 million as of December 31, 2020.

Conference Call and Webcast Information

Lexicon management will hold a live conference call and webcast today at 8:00 am ET / 7:00 am CT to review its financial and operating results and to provide a general business update. The dial-in number for the conference call is 888-645-5785 (U.S./Canada) or 970-300-1531 (international). The conference ID for all callers is 8051406. The live webcast and replay may be accessed by visiting Lexicon’s website at www.lexpharma.com/investors. An archived version of the webcast will be available on the website for 14 days.

On February 28, 2022 Heidelberg Pharma AG (FSE: HPHA) and Huadong Medicine Co., Ltd., Hangzhou, China, (SZ 000963; Huadong) reported that the companies have entered into a strategic partnership with the signing of an exclusive licensing agreement as well as an investment agreement (Press release, Heidelberg Pharma, FEB 28, 2022, View Source [SID1234609125]). The agreements were concluded with wholly owned subsidiaries of Huadong, one of the leading pharmaceutical companies in China with a focus on oncology and ADC research, development and commercialization.

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Dr. Jan Schmidt-Brand, CEO and CFO of Heidelberg Pharma, commented: "We are excited to enter this major partnership with Huadong. Through this strategic collaboration, we will gain another valuable and reliable long-term investor who fully supports our strategy to become a global ADC player, and we will be able to speed up our product development and broaden our pipeline. We are convinced that our partner’s strong development and commercialization expertise and knowledge of Asia will both shorten the time to market and maximize the commercial opportunity for our ATAC products in this important territory."

Mr. Liang Lu, Chairman of the Board and CEO of Huadong Medicine, added: "Heidelberg Pharma is an emerging leader in the ADC space. We are pleased to partner with Heidelberg Pharma and bring the best ADC products to the cancer patients in Asia. The collaboration further strengthens Huadong’s ADC portfolio and expands our ADC R&D capabilities. Huadong will contribute Asian patients to global clinical trials to help accelerate products development. We are also committed to supporting Heidelberg Pharma to 1 Asia (excluding Japan, India, Pakistan, Sri Lanka): People’s Republic of China, Hong Kong, Macao, Taiwan, South Korea, Indonesia, Singapore, The Philippines, Thailand, Bangladesh, Bhutan, Brunei, Myanmar, Cambodia, Laos, Malaysia, Maldives, Mongolia, Nepal and Vietnam 2 dievini Hopp BioTech holding GmbH & Co. KG 2/4 become a world ADC leader, by the substantial equity investment and access to Huadong’s ADC ecosystem."

Prof. Dr. Christof Hettich, Chairman of the Supervisory Board of Heidelberg Pharma and Managing Partner of dievini, said: "I am delighted that the Heidelberg Pharma team has entered into this strategic partnership with a strong Asian partner and new shareholder who shares the Company’s vision. We have been supporting Heidelberg Pharma since 2004 and are happy to see that their legacy assets have been developing nicely through partnerships and the new ATAC projects have been generating high interest from pharma companies. The dievini team is looking forward to the clinical development of the pipeline with the goal of bringing new, much-needed treatment options to cancer patients."

The strategic partnership includes the following agreements:

ATAC licensing agreement
• Heidelberg Pharma has granted Huadong exclusive development and commercialization rights for HDP-101 (BCMA-ATAC) and HDP-103 (PSMA-ATAC) for Asia1 and is eligible to receive an upfront payment of USD 20 million (EUR 17.5 million) and milestone payments of up to USD 449 million (EUR 400 million), as well as tiered royalties ranging from single to low double digit percentages for each candidate.
• Heidelberg Pharma has granted Huadong an exclusive option for the pre-IND research candidates HDP-102 (CD37-ATAC) and HDP-104 (undisclosed target) in Asia1 with a total deal value of up to USD 461 million (EUR 410 million), plus tiered royalties ranging from single to low double digit percentages for each candidate.
• Huadong also has right of first negotiation to license the next two ATAC candidates for Asia1.
• Huadong becomes the strategic partner in Asia for Heidelberg Pharma’s product development.

Investment agreement
• Huadong intends to make an equity investment in Heidelberg Pharma totaling EUR 105 million, representing 35% of total shares outstanding after the transaction, consisting of a rights issue and a share transfer as outlined below, has taken place.
• Heidelberg Pharma is planning a capital increase in the form of a rights issue of up to EUR 80 million, issuing up to 12,408,649 shares at EUR 6.44 per share, the price of the last funding round in April 2021. The rights issue will be based on a prospectus and use authorized capital. The approval of the prospectus for the rights offering by BaFin3 will be published in connection with the granting of all other necessary regulatory approvals. Further details of the capital increase will be published in due time. 3 Bundesanstalt für Finanzdienstleistungsaufsicht (Federal Financial Supervisory Authority) 3/4
• Huadong plans to acquire up to 26% of Heidelberg Pharma shares outstanding in the context of the rights issue. To achieve this percentage, the main shareholder dievini and related entities have agreed to transfer their subscription rights to Huadong, and Huadong will assume any unsubscribed shares in the rights issue. Huadong will purchase the necessary number of existing shares from dievini to reach 35% of total shares outstanding following the capital increase.
• The acquisition of shares by Huadong is subject to certain closing conditions, such as foreign trade clearance, Huadong’s exemption from the obligation to make a mandatory offer by BaFin, as well as foreign direct investment (ODI) approval required under Chinese law.
• The closing conditions must generally be satisfied until 27th August 2022 (Long Stop Date). If the necessary public approvals have not been granted by 27th July 2022, Huadong is entitled to extend the Long Stop Date until 27th October 2022, provided that Huadong grants a 12-month loan to the Company in the amount of EUR 10 million at the prevailing market interest rate. dievini would also grant a loan to the Company with the same terms as the loan from Huadong, under the framework of the financing commitment by dievini announced on 17th February 2022.
• If the approvals are not granted by the Long Stop Date, then no shares will be issued to or acquired by Huadong. However, dievini might consider participating in the rights issue and exercise a part of its subscription rights to fulfil partly or in full its financing commitment announced on 17th February 2022.

Conference call invitation
Heidelberg Pharma will host a conference call and live audio webcast to discuss the new partnership on Monday, 28th February 2022, at 1:00 pm CET, which will include a Q&A session. Participants may ask questions by phone or online via the Q&A chat window.

On February 28, 2022 FibroGen, Inc. (NASDAQ: FGEN) reported financial results for the fourth quarter and full year 2021 and provided an update on the company’s recent developments (Press release, FibroGen, FEB 28, 2022, View Source [SID1234609124]).

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"We are excited to advance pamrevlumab in three high value indications – completing enrollment in our LAPIS and LELANTOS-1 Phase 3 studies, and expecting to complete enrollment of the ZEPHYRUS-1 Phase 3 study in idiopathic pulmonary fibrosis in the next few weeks," said Enrique Conterno, Chief Executive Officer, FibroGen. "In China, roxadustat had a strong 2021 performance and after inclusion in the updated NRDL, we are off to a good start in 2022."

Recent Developments and Key Events:

Following the European Commission approval of EVRENZO (roxadustat) for the treatment of adult patients with symptomatic anemia associated with chronic kidney disease (CKD), Astellas has launched EVRENZO in Germany, the United Kingdom, Netherlands, Austria, and the Nordic countries.
Completed enrollment of the LAPIS Phase 3 clinical trial of pamrevlumab in patients with locally advanced unresectable pancreatic cancer (LAPC).
Completed enrollment of the LELANTOS-1 Phase 3 clinical trial of pamrevlumab in patients with Duchenne muscular dystrophy (DMD).
Exercised option to exclusively license HiFiBiO’s CCR8 drug program to advance next-generation therapies for patients with solid tumors.
China:

Roxadustat net transfer price from sales to the distribution entity (JDE) jointly owned by FibroGen and AstraZeneca was $12.2 million for the fourth quarter. From the net transfer price, FibroGen defers a certain portion for revenue recognition purposes under U.S. GAAP. FibroGen reported $5.5 million in roxadustat net product revenue for the quarter.
In the fourth quarter of 2021, China’s National Healthcare Security Administration renewed the listing of roxadustat on the National Reimbursement Drug List (NRDL).
Due to the price reduction associated with the NRDL listing renewal, we have updated our estimates and reflected a cumulative adjustment in our revenue in the fourth quarter.
Fourth quarter total roxadustat net sales in China1 of $32.0 million2 by FibroGen and the JDE compared to $29.2 million in the fourth quarter of 2020.
Full year 2021 total roxadustat net sales in China1 of $186.1 million by FibroGen and the JDE compared to $72.5 million in the full year 2020.
Roxadustat continues to be the number one brand based on value share in the anemia of CKD market in China.
Upcoming Milestones:

Expect to complete enrollment in the ZEPHYRUS-1 Phase 3 study of pamrevlumab in idiopathic pulmonary fibrosis (IPF) in the next few weeks.
Interim analysis of event free survival of the LAPIS Phase 3 study of pamrevlumab in LAPC expected to be conducted in 2Q 2022.
Topline data from the LELANTOS-1 Phase 3 study of pamrevlumab in DMD expected 1H 2023.
Topline data from the ZEPHYRUS-1 Phase 3 study of pamrevlumab in IPF expected mid-2023.
Topline data from the MATTERHORN Phase 3 study of roxadustat in anemia of myelodysplastic syndromes (MDS) expected 2H 2022 / 1H 2023.
Corporate:

Implemented a plan to reduce our projected expenses by approximately $100 million per year, for each of the next 3 years, compared to our previous internal plans.
Financial:

Total revenue for the fourth quarter of 2021 was $16.5 million, as compared to $65.0 million for the fourth quarter of 2020.
Total revenue for 2021 was $235.3 million as compared to $176.3 million in 2020.
Net loss for the fourth quarter of 2021 was $134.1 million, or $1.45 net loss per basic and diluted share, compared to a net loss of $58.6 million, or $0.64 net loss per basic and diluted share one year ago.
Net loss for the year was $290.0 million, or $3.14 net loss per basic and diluted share, compared to a net loss of $189.3 million, or $2.11 net loss per basic and diluted share one year ago.
At December 31, 2021, FibroGen had $590.4 million in cash – defined as cash, cash equivalents, investments, and accounts receivable.
Based on our latest forecast, we estimate our 2022 ending cash to be in the range of $270 to $300 million.
1 Total roxadustat net sales in China includes sales made by the distribution entity as well as FibroGen China’s direct sales, each to its own distributors. The distribution entity jointly owned by AstraZeneca and FibroGen is not consolidated into FibroGen’s financial statements.
2 As a result of the price reduction associated with the NRDL listing renewal, the roxadustat net sales for the fourth quarter of 2021 reflected a one-time adjustment driven by a revaluation of channel inventory.

Conference Call and Webcast Details
FibroGen will host a conference call and webcast today, Monday, February 28, 2022, at 5:00 p.m. Eastern Time (2:00 p.m. Pacific Time) to discuss financial results and provide a business update. A live audio webcast of the call may be accessed in the investor section of the Company’s website, www.fibrogen.com. To participate in the conference call by telephone, please dial 1 (877) 658-9081 (U.S. and Canada) or 1 (602) 563-8732 (international), reference the FibroGen fourth quarter 2021 financial results conference call, and use confirmation number 1795663. A replay of the webcast will be available shortly after the call for a period of 7 days. To access the replay, please dial 1 (855) 859-2056 (domestic) or 1 (404) 537-3406 (international) and use passcode 1795663.

About Pamrevlumab
Pamrevlumab is a first-in-class antibody developed by FibroGen that inhibits the activity of connective tissue growth factor (CTGF), an important biological mediator in fibrotic and proliferative disorders. Pamrevlumab is in Phase 3 clinical development for the treatment of idiopathic pulmonary fibrosis (IPF), locally advanced unresectable pancreatic cancer (LAPC), and Duchenne muscular dystrophy (DMD). For information about pamrevlumab studies currently recruiting patients, please visit www.clinicaltrials.gov.

About Roxadustat
Roxadustat, an oral medication, is the first in a new class of medicines comprising HIF-PH inhibitors that promote erythropoiesis, or red blood cell production, through increased endogenous production of erythropoietin, improved iron absorption and mobilization, and downregulation of hepcidin. Roxadustat is in clinical development for anemia of chronic kidney disease (CKD) and anemia associated with myelodysplastic syndromes (MDS), and for chemotherapy-induced anemia (CIA).

Roxadustat is approved in European Union (EU) member states, including the European Economic Area (EEA) countries, as well as in Japan, China, Chile, and South Korea for the treatment of anemia of CKD in adult patients on dialysis (DD) and not on dialysis (NDD). Several other licensing applications for roxadustat have been submitted by partners, Astellas and AstraZeneca to regulatory authorities across the globe, and are currently under review.

Astellas and FibroGen are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in territories including Japan, Europe, Turkey, Russia and the Commonwealth of Independent States, the Middle East, and South Africa. FibroGen and AstraZeneca are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in the U.S., China, other markets not licensed to Astellas.

On February 28, 2022 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported business highlights and financial results for the fourth quarter and full year ended December 31, 2021 (Press release, Fate Therapeutics, FEB 28, 2022, View Source [SID1234609123]).

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"We have begun 2022 with strong clinical and regulatory momentum driving our off-the-shelf, iPSC-derived NK cell programs in relapsed / refractory lymphoma, and look forward to working with the FDA under the Regenerative Medicine Advanced Therapy designation to accelerate therapeutic development in areas of significant unmet need, such as patients who have progressed following autologous CAR T-cell therapy, and to bringing transformative cell therapies to patients in the community setting including as part of early-line treatment," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We maintain a strong financial position and are poised in 2022 to achieve key clinical milestones and data read-outs across our wholly-owned disease franchises, to extend our leadership in the manufacture and CMC of iPSC-derived cell therapies with the launch of our second cGMP manufacturing facility, and to bring new multiplexed-engineered NK and T-cell product candidates to patients."

B-cell Malignancy Disease Franchise

FT596+R Multi-dose, Multi-cycle Escalation Cohort Enrolling at 900 Million Cells per Dose. The first patients have been treated with a multi-dose, multi-cycle treatment schedule of FT596 in combination with rituximab (FT596+R) for relapsed / refractory (r/r) B-cell lymphoma (BCL) in the dose-escalation stage of the Company’s multi-center Phase 1 study. FT596 is being administered on Day 1 and Day 15 at 900 million cells per dose in each cycle, with the potential to dose escalate to 1.8 billion cells per dose. The Company plans to initiate multiple disease-specific, dose-expansion cohorts in the first quarter of 2022.
Positive Interim Phase 1 Clinical Data Reported for FT596+R Single-dose Escalation Cohorts. At the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December, the Company presented positive interim Phase 1 clinical data from the single-dose escalation cohorts of its FT596 Phase 1 study. In the second (90 million cells; n=4), third (300 million cells; n=6), and fourth (900 million cells; n=6) single-dose escalation cohorts of FT596+R, 11 of 16 patients (69%) achieved an objective response (ORR), including nine patients (56%) who achieved a complete response (CR), on Day 29 as assessed by PET-CT scan per Lugano 2014 criteria. As of the data cutoff date of October 11, 2021, of the 10 patients in the second and third single-dose escalation cohorts, six patients responded and were evaluable for duration of response assessment. Five patients, all of whom were treated with a second FT596+R single-dose cycle, continued in ongoing response at a median follow-up of 4.6 months, including two patients in ongoing CR at 6.0 and 10.8 months; and one patient, who was treated with a second FT596+R single-dose cycle, reached six months in CR and subsequently had disease progression at 6.7 months. Treatment with FT596+R was well tolerated, with two low-grade adverse events (one Grade 1, one Grade 2) of cytokine release syndrome (CRS) and no adverse events of immune effector cell-associated neurotoxicity syndrome (ICANS) or graft-versus-host disease (GVHD).
RMAT Designation Granted by FDA for FT516 in R/R DLBCL. In December, the Company announced that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to FT516 for the treatment of r/r diffuse large B-cell lymphoma (DLBCL). RMAT designation is designed to expedite the development and review of regenerative medicine therapies that have demonstrated the potential to address an unmet medical need based on preliminary clinical evidence, and allows for early interactions with the FDA, including to discuss efficient drug development and pathways for accelerated approval. The Company plans to discuss its manufacturing, CMC, and pivotal study design with the FDA during the first half of 2022. In its ongoing FT516 Phase 1 clinical trial, the Company is currently enrolling patients in three disease-specific expansion cohorts at 900 million cells per dose, each of which uses cyclophosphamide (Cy) and fludarabine (Flu) as conditioning chemotherapy: patients with r/r aggressive lymphomas who have previously been treated with CD19-targeted chimeric antigen receptor (CAR) T-cell therapy; patients with r/r aggressive lymphomas who are naïve to treatment with CD19-targeted CAR T-cell therapy; and patients with r/r follicular lymphoma. In addition, the Company is also enrolling patients in a fourth expansion cohort, without Cy/Flu conditioning chemotherapy, adding FT516 to rituximab plus bendamustine (R-Benda), a standard-of-care treatment regimen for BCL.
Positive FT516 Interim Phase 1 Clinical Data Reported in Multi-dose, Multi-cycle Escalation Cohorts. At the ASH (Free ASH Whitepaper) Annual Meeting in December, the Company highlighted positive interim Phase 1 clinical data of FT516 in combination with rituximab from the multi-dose, multi-cycle escalation cohorts for the treatment of r/r BCL. Of the 18 patients treated at ≥90 million cells, 10 patients were naïve to treatment with autologous CD19-targeted CAR T-cell therapy, eight of whom achieved an ORR (80%), including five patients who achieved a CR (50%); and eight patients were previously treated with autologous CD19-targeted CAR T-cell therapy, three of whom achieved a CR (38%). All 11 responding patients continued in ongoing response at three months following initiation of treatment (61%), and eight patients continued in ongoing response (44%) at a median follow-up of 8.3 months. The multi-dose, multi-cycle treatment regimen was well tolerated, with no adverse events of CRS, ICANS, or GVHD.
Initial FT819 Dose-Escalation Cohort Cleared with No DLTs for R/R BCL in Landmark Phase 1 Study of Off-the-shelf, iPSC-derived CAR T-cell Therapy. FT819 is the first-ever T-cell therapy manufactured from a clonal master induced pluripotent stem cell (iPSC) line to undergo clinical investigation. The product candidate’s clonal master iPSC line is created from a single iPSC that has a novel CD19-targeted 1XX CAR construct (1XX-CAR19) integrated into the T-cell receptor alpha constant (TRAC) locus, ensuring complete bi-allelic disruption of T-cell receptor expression and promoting uniform CAR expression. In the first FT819 single-dose escalation cohort (90 million cells) for r/r BCL in the Company’s Phase 1 study of FT819, there were no dose-limiting toxicities (DLTs) and no FT819-related Grade ≥3 adverse events. Enrollment is now ongoing in three treatment regimens for r/r BCL: single-dose cohort at 180 million cells; single-dose cohort at 90 million cells administered with low-dose IL-2 cytokine support; and three-dose cohort at 30 million cells per dose. In addition, enrollment is ongoing in the first single-dose escalation cohorts (90 million cells) for r/r chronic lymphocytic leukemia (CLL) and for r/r acute lymphoblastic leukemia (ALL).
AML Disease Franchise

Enrollment Ongoing in Two FT538 Phase 1 Clinical Trials. The Company’s Phase 1 study of FT538 as monotherapy and an investigator-initiated study of FT538 in combination with the CD38-targeted monoclonal antibody daratumumab are each currently enrolling patients in the second multi-dose escalation cohort (300 million cells per dose) for r/r acute myeloid leukemia (AML). The combination of FT538 with daratumumab is designed to exploit the product candidate’s proprietary high-affinity, non-cleavable (hnCD16) receptor and CD38 knock-out (CD38KO) to recognize, bind, and kill CD38+ leukemic blasts through antibody-dependent cellular cytotoxicity (ADCC).
Multiple Myeloma Franchise

First Patients Treated in FT576 Phase 1 Study. FT576 is derived from a clonal master iPSC line engineered with four functional components (CAR-BCMA + hnCD16 + IL-15RF + CD38KO) designed to enable multi-antigen targeting of myeloma cells, augment ADCC, promote NK cell activation without exogenous cytokine support, enhance NK cell persistence and prevent anti-CD38 monoclonal antibody-induced fratricide. The Company has treated the first patients in its multi-center Phase 1 clinical trial to assess single-dose and multi-dose treatment regimens of FT576 as monotherapy and in combination with daratumumab for the treatment of r/r multiple myeloma (MM).
Phase 1 Study of FT538+D Cleared Initial Dose-Escalation Cohort with No DLTs. The Phase 1 clinical trial is designed to assess three once-weekly doses of FT538 in combination with daratumumab (FT538+D) for r/r MM. There were no DLTs observed in the first multi-dose escalation cohort (100 million cells per dose), and enrollment is now ongoing in the second multi-dose escalation cohort (300 million cells per dose) at eight U.S. sites.
Solid Tumor Franchise

First Patients Treated in Phase 1 Study of FT538 in Combination with Monoclonal Antibody Therapy. The Company has treated the first patients in its multi-center Phase 1 clinical trial to assess the safety and activity of three once-weekly doses of FT538 in combination with monoclonal antibody therapy for advanced solid tumors. The clinical protocol includes combination with each of four monoclonal antibodies: EGFR-targeted cetuximab; HER2-targeted trastuzumab; PD1-targeted pembrolizumab; and PDL1-targeted avelumab. Each patient is eligible to receive up to two FT538 treatment cycles, and additional FT538 treatment cycles may be administered to patients that achieve initial clinical response. These off-the-shelf treatment cycles are designed to be administered in the outpatient setting.
IND Allowed for FT536 CAR MICA/B-targeted NK Cell Product Candidate. In December 2021, the FDA cleared an Investigational New Drug (IND) application for FT536, the Company’s off-the-shelf, multiplexed-engineered, iPSC-derived NK cell product candidate, which incorporates a novel CAR targeting the major histocompatibility complex (MHC) class I related proteins A (MICA) and B (MICB). High expression of MICA and MICB proteins (MICA/B), which is induced by cellular stress, damage or transformation, has been reported on many solid tumors, although the proteolytic shedding of the α1 and α2 domains of MICA/B is recognized as a common tumor escape mechanism. The clonal master iPSC bank for FT536 was created from a single iPSC engineered with four functional elements, including the novel CAR which uniquely targets the α3 domain of MICA/B and is designed to overcome tumor escape mechanisms mediated by loss of MHC Class I expression and proteolytic shedding. The Company is preparing to initiate a multi-center Phase 1 clinical trial to assess a multi-dose, multi-cycle treatment schedule of FT536 as monotherapy and in combination with monoclonal antibody therapy for advanced solid tumors.
Other Corporate Highlights

Preclinical Milestone Reached for Second Product Candidate under Janssen Collaboration. In January 2022, Janssen elected to initiate IND-enabling activities for a second iPSC-derived CAR NK cell product candidate incorporating a Janssen proprietary antigen binding domain, triggering the payment of a milestone fee to the Company under the collaboration.
Key Executive Promotions. The Company promoted Yu-Waye (Wayne) Chu, M.D. to Chief Medical Officer and Jerome Bressi, Ph.D. to Senior Vice President, Regulatory Affairs and Quality Assurance. Dr. Chu joined the Company in 2019 from Genentech, where he led early clinical development of cancer agents spanning multiple therapeutic platforms, including polatuzumab vedotin (anti-CD79b antibody drug conjugate), mosunetuzumab (CD20/CD3 bispecific antibody), and tiragolumab (anti-TIGIT monoclonal antibody). Dr. Bressi joined the Company in 2018 and has played an integral role in pioneering the clinical investigation of iPSC-derived cell therapy in the United States, and leads the Company’s regulatory strategies and interactions with the FDA for its iPSC product platform.
Fourth Quarter 2021 Financial Results & 2022 Guidance

Cash & Investment Position: Cash, cash equivalents and investments as of December 31, 2021 were $716.6 million. Cash use in the fourth quarter included a $20 million milestone payment to Memorial Sloan Kettering Cancer Center associated with the treatment of the first patient with FT819.
Total Revenue: Revenue was $17.1 million for the fourth quarter of 2021, which was derived from the Company’s collaborations with Janssen and Ono Pharmaceutical.
R&D Expenses: Research and development expenses were $69.5 million for the fourth quarter of 2021, which includes $9.4 million of non-cash stock-based compensation expense.
G&A Expenses: General and administrative expenses were $16.9 million for the fourth quarter of 2021, which includes $5.2 million of non-cash stock-based compensation expense.
Shares Outstanding: Common shares outstanding were 95.7 million, and preferred shares outstanding were 2.8 million, as of December 31, 2021. Each preferred share is convertible into five common shares.
2022 Guidance: For the full year ending December 31, 2022, the Company expects its GAAP Loss from Operations to be between $335 million to $365 million, which loss includes stock-based compensation expense, and its cash use to be between $290 million to $315 million, which use excludes any amounts that may be received under its collaborations with Janssen and Ono in connection with the achievement of development milestones. The Company expects its cash, cash equivalents, and investments to exceed $400 million at year-end 2022.
Today’s Conference Call and Webcast

The Company will conduct a conference call today, Monday, February 28, 2022 at 5:00 p.m. ET to review financial and operating results for the quarter and full year ended December 31, 2021. In order to participate in the conference call, please dial (877) 303-6235 (domestic) or (631) 291-4837 (international) and refer to conference ID 1888465. The live webcast can be accessed under "Events & Presentations" in the Investors section of the Company’s website at www.fatetherapeutics.com. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT516
FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of therapeutic antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in a multi-dose Phase 1 clinical trial as a monotherapy for the treatment of relapsed / refractory acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of relapsed / refractory B-cell lymphoma (NCT04023071).

About FT596
FT596 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that targets B-cell antigen CD19; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; and an IL-15 receptor fusion (IL-15RF) that augments NK cell activity. In preclinical studies of FT596, the Company has demonstrated that dual activation of the CAR19 and hnCD16 targeting receptors enhances cytotoxic activity and prevents antigen escape, indicating that multi-antigen engagement may elicit a deeper and more durable response. Additionally, in a humanized mouse model of lymphoma, FT596 in combination with the anti-CD20 monoclonal antibody rituximab showed enhanced killing of tumor cells in vivo as compared to rituximab alone. FT596 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell lymphoma as a monotherapy and in combination with rituximab, and for the treatment of relapsed / refractory chronic lymphocytic leukemia (CLL) as a monotherapy and in combination with obinutuzumab (NCT04245722).

About FT819
FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease. FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia. FT819 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).

About FT538
FT538 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three functional components: a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments. FT538 is designed to enhance innate immunity in cancer patients, where endogenous NK cells are typically diminished in both number and function due to prior treatment regimens and tumor suppressive mechanisms. In preclinical studies, FT538 has shown superior NK cell effector function, as compared to peripheral blood NK cells, with the potential to confer significant anti-tumor activity to patients through multiple mechanisms of action. FT538 is being investigated in a multi-dose Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and in combination with daratumumab, a CD38-targeted monoclonal antibody therapy, for the treatment of multiple myeloma (NCT04614636). FT538 is also being investigated in a multi-dose Phase 1 clinical trial in combination with one of an array of tumor-targeting monoclonal antibodies for the treatment of advanced solid tumors (NCT05069935).

About FT576
FT576 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with four functional components: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that targets B-cell maturation antigen (BCMA); a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments. In preclinical studies, FT576 has demonstrated that the high-avidity binding of the BCMA-targeted CAR construct enables sustained tumor control in against various multiple myeloma cell lines, including in long-term in vivo xenograft mouse models. Additionally, in combination with daratumumab, FT576 has shown complete tumor clearance and improved survival compared to primary BCMA-targeted CAR T cells in a disseminated xenograft model of multiple myeloma. FT576 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory multiple myeloma as a monotherapy and in combination with daratumumab (NCT05182073).