(Picture: Paul Hastings, CEO & President of Nkarta Therapeutics)
안녕하세요 보스턴 임박사입니다.
지난번에 CAR-NK Cell Therapy 회사인 NKarta Therapeutics에 대해 얘기를 하다가 2019년까지의 경과까지 마쳤습니다.
BIOTECH (56) – Nkarta Therapeutics: CAR-NK의 미래 (1부)
2020년에 NKarta Therapeutics는 IPO를 하게 됩니다. $252 Million 규모의 굉장히 큰 IPO였습니다.
Nkarta Announces Pricing of Initial Public Offering – Globe Newswire 7/10/2020
Nkarta, Inc. (Nasdaq: NKTX), a clinical-stage biopharmaceutical company developing engineered natural killer (NK) cell therapies to treat cancer, today announced the pricing of its initial public offering of 14,000,000 shares of common stock at a public offering price of $18.00 per share. Nkarta anticipates total gross proceeds of approximately $252.0 million, before deducting underwriting discounts and commissions and other offering expenses. The shares are expected to begin trading on The Nasdaq Global Select Market on July 10, 2020 under the ticker symbol “NKTX.” All shares of common stock are being offered by Nkarta. The offering is expected to close on or about July 14, 2020, subject to customary closing conditions. In addition, Nkarta has granted the underwriters a 30-day option to purchase up to an additional 2,100,000 shares of common stock at the initial public offering price.
Cowen, Evercore ISI, Stifel and Mizuho Securities are acting as joint book-running managers for the offering.
2021년에 NKarta Therapeutics는 CRISPR Therapeutics와 전략적 제휴를 하게 됩니다.
CRISPR therapeutics, Nkarta pen new cutting-edge cancer tech research pact – Fierce Biotech 5/7/2021
Two next-gen biotech pioneers in natural killer cell therapies and gene editing are coming together to battle cancer.
Under the new deal, financials of which were not disclosed, gene-editing specialist CRISPR Therapeutics and NK cell therapy startup Nkarta will work together to seek out CRISPR/Cas9 gene-edited cell therapies for cancer.
Under the agreement, the companies will both develop and sell two CAR NK cell candidates, one targeting the CD70 tumor antigen and the “other target to be determined,” according to a joint statement.
Nkarta also nabs a license to CRISPR gene editing tech, specifically to edit five gene targets in an “unlimited number” of its own NK cell therapy products. Both biotechs will equally share all R&D costs and profits under the collab products.
Specifics on costs, upfronts, biobucks or targets were not shared by the two companies.
This builds on deals CRISPR has already penned over the years, including most recently an updated pact with Vertex as the biotech continues, alongside its many rivals, to find a way to make the latent promise of gene editing work in the clinic and look ahead to potential first approvals in the future.
“By bringing together CRISPR Therapeutics’ and Nkarta’s highly complementary expertise and proprietary platforms we plan to accelerate the development of potentially groundbreaking genome engineered NK cell therapies,” said Samarth Kulkarni, Ph.D., CEO at CRISPR Tx. “This collaboration broadens the scope of our efforts in oncology cell therapy, and expands our efforts to discover and develop novel cancer therapies for patients.”
Nkarta has had a good run in recent months; last year, it got off a $252 million IPO, one of the biggest life science initial public offerings of 2020, coming off a hefty $114 million B round the year before.
Last year, the company dosed its first patient in the phase 1 trial of its leading asset, NKX101, a first-in-class investigational NK cell cancer immunotherapy engineered to express a chimeric antigen receptor (CAR) targeting NKG2D ligand in certain blood cancers. Nkarta believes using NK cells could clear the hurdles that have limited the success of CAR-T therapies in blood cancers.
“Uniting the best-in-class gene editing solution and allogeneic T cell therapy expertise of CRISPR with Nkarta’s best-in-class CAR NK cell therapy platform will be a major advantage to advancing the next wave of transformative cancer cell therapies,” added Paul Hastings, president and chief at Nkarta.
“With this partnership, Nkarta can systematically apply world-class gene editing across our entire pre-clinical pipeline going forward. CRISPR’s deep understanding of CD70 biology and experience in allogeneic T cell clinical development can accelerate the development of early-stage Nkarta programs, to deliver innovative treatments to patients that much faster.”
Nkarta Announces Proposed Public Offering of Common Stock – Biospace Apr 25, 2022
Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer cell therapies to treat cancer, today announced that it has commenced a proposed underwritten public offering to issue and sell $150 million of shares of its common stock. The Company also intends to grant the underwriters a 30-day option to purchase up to an additional $22.5 million of shares of its common stock on the same terms and conditions. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed or as to the actual size or terms of the offering. All shares in the offering are to be issued and sold by Nkarta.
Nkarta intends to use the net proceeds from the offering to fund the continued clinical development of NKX101 and NKX019, preclinical studies for research stage programs and the continued buildout of internal manufacturing capabilities, and for working capital and for general corporate purposes.
Cowen, SVB Securities and Evercore ISI are acting as joint book-running managers for the offering.
2022년 12월에 Nkarta는 Clinical Update를 보고했습니다. NKX019는 최고용량인 1.5 Billion cells (3 Doses) 일 때, 4명 중 3명에서 CR과 ORR을 얻어서 초기지만 결과는 나쁘지 않았습니다.
그리고 6개월 후에 다시 Clinical Update를 했습니다.
Fate Therapeutics의 NK Cell Therapy가 실패하면서 Nkarta의 CAR-NK oncology program에 위기가 감지되기 시작합니다. Class action인 것으로 보이죠. 2023년 10월에 Lupus로 NKX019의 임상시험을 할 수 있게 되면서 주가가 100% 이상 급등하였지만 임직원 구조조정이 뒤따랐습니다.
Nkarta wants cell therapy to go beyond cancer and has been given the FDA green light to move forward with a CAR NK candidate in human trials for lupus—news that sent the company’s stock soaring 112%.
“Autoimmune patients have limited options these days, and those options that they have are often toxic, or hard to take—hard to live with,” Nkarta President and CEO Paul Hastings told Fierce Biotech in an interview. “What we’re hoping to do is to move that patient population into an easier to take, patient-friendly therapy.”
After Nkarta said Oct. 17 that the FDA is allowing a human test of NKX019 in lupus nephritis, the company’s stock rose from $1.47 per share at market open to $3.14 by the end of the day. The allogeneic, CD19-directed CAR NK cell therapy candidate is already being tested out in a phase 1 trial for patients with B-cell malignancies, with top-line data expected next year.
In the shadows of Nkarta’s big announcement lies a workforce reduction, with the company set to lay off 18 employees, according to Securities and Exchange Commission documents filed Oct. 16.
The cuts—which will take place “across the board,” according to Hastings—align with the company’s mission to focus on its later-stage programs, including NKX019.
The layoffs are an attempt to save cash and support operations through 2024, when Nkarta anticipates multiple clinical data readouts. Alongside other cost-cutting measures, the layoffs are expected to extend the company’s cash runway by a year into 2026.
As of Sept. 30, the biotech had $278.4 million on hand.
Lupus nephritis impacts the kidneys specifically and is one of the most severe forms of systemic lupus erythematosus (SLE), an autoimmune disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage.
“We’re actively looking at other autoimmune diseases,” Nkarta Chief Medical Officer David Shook, M.D., told Fierce. “There’s lots of diseases that are caused by autoantibodies, not just lupus. And we think that targeting B cells could be helpful in those as well.”
Their theory is supported by a German study among five patients with SLE who received CAR-T cells, Shook said. The study, published last year in Nature Medicine, found all five patients were in remission after three months and that remission was maintained even after the reappearance of B cells beyond three months.
Nkarta’s new trial will be a multicenter, open-label, dose-escalation study in patients with refractory lupus nephritis. Patients will receive a three-dose cycle of NKX019 on three separate occasions, each a week apart, after lymphodepletion with cyclophosphamide, an immunosuppressive drug with an established safety profile in lupus that is also used as chemotherapy. The trial is expected to include up to 12 patients, with the first patient set to enroll in the first half of 2024.
Nkarta is also partnering with Lupus Therapeutics, a clinical research affiliate of the Lupus Research Alliance, to help speed up NKX019’s development.
Current lupus treatments include GSK’s SLE drug Benlysta, a biologic therapy approved by the FDA in 2011 that brought in more than $1 billion last year, and AstraZeneca’s Saphnelo, an IV infusion that snagged approval for patients with SLE in 2021.
“Right now, what’s on the market are largely ineffective and require, more or less, lifetime treatment,” Shook said.
Bringing cell therapy outside of cancer may be seen as somewhat inaccessible right now, Shook said, adding that there’s “lots of legwork.” However, if NKX019 were to reach the market, Nkarta expects its off-the-shelf availability to reduce patient burden and eliminate the need for costly infrastructure and treatment delays currently associated with autologous cell therapies. The asset is active immediately, is self-sustaining and doesn’t require large cytokine surges from preparative chemotherapy.
Nkarta’s CAR NK blood cancer candidate has again stalled after making a speedy start. The response rate fell away sharply in the latest update, mirroring what happened in an earlier cohort and driving the cell therapy developer to mothball the program.
The off-the-shelf candidate, NKX101, consists of CAR NK cells engineered to express a NKG2D receptor. Through the engineering, Nkarta tried to boost the longevity, potency and activity of NK cells and create a cell therapy that is effective in a range of blood cancers and solid tumors. The drug candidate has failed to live up to those ambitions, despite twice showing promise in small numbers of patients.
Nkarta reported four complete responses in six acute myeloid leukemia (AML) last year, encouraging it to push ahead. Yet, the next 14 patients only included one complete response. The crumbling response rate, which fell from 67% to 25%, has prompted Nkarta to deprioritize NKX101.
The biotech is yet to completely give up on the asset, with CEO Paul Hastings saying in a statement that the team will “evaluate options for optimizing future study design, dosing schedule and manufacturing.” But Nkarta sees its autoimmune candidate as a better use of the $250.9 million it had at the end of last year. The biotech still expects its cash to last into 2026, a runway made possible by layoffs last year.
William Blair analysts said they view the pipeline reprioritization “positively” in a research note, telling inventors that they believe the shift “accurately reflects increased investor enthusiasm for the potential of allogeneic cell therapies for autoimmune diseases and waning interest in NKX101, particularly in light of the disappointing efficacy in AML.”
The falling response rate echoes what happened in an earlier cohort. In 2022, Nkarta said that three of the first five AML patients to receive the highest doses of NKX101 had complete responses and raised $230 million on the back of the news. However, the biotech only saw one more complete response in the next 13 high-dose patients.
Nkarta responded to the first collapse of its response rate by switching its focus to a cohort that received a different conditioning regimen. We now know the 67% response rate seen in that cohort was another mirage, not a sign that Nkarta had cracked the CAR NK puzzle by giving cytarabine, a chemotherapy drug, before the cell therapy.
The failure to find a path forward for the cancer candidate leaves Nkarta’s hopes resting on NKX019, the CD19-directed CAR NK prospect that the FDA cleared for testing in lupus nephritis last year. Developers of CD19 cell therapies have surged into lupus over the past 18 months, attracted by data that suggest the treatments may cure the autoimmune disease.
2024년 2월에 발표한 Corporate Presentation에 보면 NKX019의 Lupus Nephritis (SLE)가 가장 앞에 나와 있습니다. Nkarta의 원천 기술이었던 NKG2D를 통한 NKX101은 임상결과가 실망스러웠기 때문에 특별히 진행할 이유가 없어졌고 과연 NKX019의 r/r NHL 결과가 어떻게 나올지도 중요한 관전 포인트가 됩니다. 결국 CAR-T와의 경쟁이지만 CAR-NK는 Allogeneic (Off-the-shelf) 이라는 장점이 있기 때문에 아직 실망하기에는 이르다고 생각합니다. 임상시험을 시작한지 얼마되지 않기 때문에 아직 데이타를 얻는데에는 시간이 좀더 걸릴 것 같습니다. 좋은 임상 결과를 얻어야 다음 펀딩도 가능하지 않을까 싶습니다.
BOSTON DR LIM 