On January 16, 2023 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported the publication in Nature Biotechnology of preclinical data showing the control of acute myeloid leukemia (AML) cells by a trifunctional NKp46-CD16a-NK cell engager (NKCE) targeting CD123 (Press release, Innate Pharma, JAN 16, 2023, View Source [SID1234626269]). The studies were conducted by Innate and Sanofi and published in Nature Biotechnology on January 12, 2023.

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The study shows that expression of CD64 on AML blasts confers resistance to anti-CD123 antibody-dependent cell cytotoxicity (ADCC) and redirecting NK cells against cancer targets through binding to CD16a and NKp46 circumvents this resistance. Moreover, through their binding to NKp46, CD123-NKCE specifically target NK cells and has potent antitumor activity against primary AML blasts; it induces NK cell activation and cytokine secretion only in the presence of AML cells. In vivo, its antitumor activity in a mouse tumor model exceeds that of the comparator anti-CD123 antibody. The efficacy of CD123-NKCE in vitro in human peripheral blood mononuclear cells and in vivo in nonhuman primates was associated with the induction of low pro-inflammatory cytokine release and no signs of toxicity.

These results support clinical development of CD123-NKCE. A Phase 1/2 clinical trial by Sanofi is ongoing, evaluating IPH6101/SAR’579 (SAR443579), the first NKp46/CD16-based CD123-targeted ANKETTM NK cell engager, in patients with relapsed or refractory acute myeloid leukemia (R/R AML), B-cell acute lymphoblastic leukemia (B-ALL) or high-risk myelodysplastic syndrome (HR-MDS).

Eric Vivier, DVM, PhD, Chief Scientific Officer of Innate Pharma:

"The activity, safety, pharmacokinetic and pharmacodynamics data provided here demonstrate the superiority of CD123-NKCEs over comparator cytotoxic antibodies in terms of antitumor activity, and their favorable safety profiles relative to T cell therapies for the treatment of AML. IPH6101/SAR’579 is a multi-specific NKCE targeting CD123 currently in a Phase 1 trial in AML sponsored by Sanofi. At Innate Pharma, we are developing a broad portfolio of NK Cell Engager programs via our proprietary platform ANKETTM that can address different types of cancer."

Valeria Fantin, Ph.D., Global Head of Oncology Research at Sanofi:

"At Sanofi, we are building a diverse oncology portfolio including next-generation NK-based assets and bringing new approaches to fighting cancer. We’re pleased with our productive collaboration with Innate Pharma, and data like this reinforce our confidence in proceeding to clinical evaluation of this novel NK cell engager."

About ANKETTM

ANKETTM (Antibody-based NK cell Engager Therapeutics) is Innate’s proprietary platform for developing next-generation, multi-specific natural killer (NK) cell engagers to treat certain types of cancer.

This versatile, fit-for-purpose technology is creating an entirely new class of molecules to induce synthetic immunity against cancer. It leverages the advantages of harnessing NK cell effector functions against cancer cells and also provides proliferation and activation signals targeted to NK cells.

Our latest innovation, the tetra-specific ANKET molecule, is the first NK cell engager technology to engage activating receptors (NKp46 and CD16), a tumor antigen and an interleukin-2 receptor (via an IL-2 variant, IL-2v) via a single molecule.

On January 16, 2023 Medivir AB (Nasdaq Stockholm: MVIR), a pharmaceutical company focused on developing innovative treatments for cancer in areas of high unmet medical need, reported that the company will participate at the Redeye Fight Cancer Day on January 19, 2023 (Press release, Medivir, JAN 16, 2023, View Source [SID1234626268]).

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CEO Jens Lindberg will present the company and its plan for the ongoing clinical study with fostroxacitabine bralpamide (fostrox) at 13.35 CET.

The presentation is live broadcasted and can be followed at the event page;
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On January 16, 2023 CARsgen Therapeutics Holdings Limited (2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, and Huadong Medicine (Hangzhou) Co., Ltd., a wholly-owned subsidiary of Huadong Medicine Co., Ltd. (Huadong Medicine; SZ: 000963), reported a collaboration for the commercialization of CARsgen’s BCMA CAR-T product CT053 in mainland China (Press release, Carsgen Therapeutics, JAN 16, 2023, View Source [SID1234626267]).

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CT053, zevorcabtagene autoleucel ("zevor-cel"), is CARsgen’s lead drug candidate and an autologous CAR T-cell product treating relapsed/refractory multiple myeloma (R/R MM). CT053 NDA was submitted to NMPA in October 2022. With strong commercial capability and network, Huadong Medicine is granted the exclusive right to commercialize zevor-cel in mainland China.

"Huadong’s extensive commercialization experience in mainland China along with their strategic goal of being a leader in the oncology therapeutic area created the opportunity for a strong, strategic and mutually beneficial partnership between our two companies," said Dr. Zonghai Li, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics Holdings Limited, "Despite advancements in recent years, there are still significant unmet medical needs for the treatment of multiple myeloma. Zevor-cel, a differentiated BCMA CAR T cell therapy, has shown promising data in clinical programs and is now under NDA priority review by NMPA. We believe this collaboration with Huadong Medicine will enhance the successful commercialization of zevor-cel in mainland China."

"CARsgen is a leading biotech company in the development of innovative cell therapies for cancer patients and has built integrated R&D and manufacturing capabilities," added Liang Lv, Chairman of Huadong Medicine. "We are excited to collaborate with CARsgen to commercialize CT053. Leveraging Huadong’s strong commercial presence in hematology, Huadong is committed to bringing CT053, an innovative and highly effective new treatment, to more R/R MM patients in China, and improve their survival and quality of life."

Under the terms of the agreement, CARsgen will receive an upfront payment of RMB200 million and is eligible to receive regulatory and commercial milestone payments up to RMB1,025 million. CARsgen will continue to be responsible for the development, regulatory approval, and manufacturing of CT053 in mainland China.

About CT053

CT053, zevorcabtagene autoleucel ("zevor-cel"), is a fully human, autologous BCMA CAR T-cell product candidate for the treatment of R/R MM. The New Drug Application (NDA) based on the phase I/II data from LUMMICAR STUDY 1 in China has been accepted by NMPA. CARsgen is conducting the phase 1b/2 LUMMICAR STUDY 2 in North America to evaluate the safety and efficacy of CT053 for R/R MM in that population. The Company also plans additional clinical trials for earlier line multiple myeloma treatment.

CT053 received Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug designations from the U.S. FDA in 2019, as well as the Priority Medicines (PRIME) and Orphan Medicinal Product designations from the European Medicines Agency (EMA) in 2019 and 2020, respectively. CT053 also received Breakthrough Therapy designation from the NMPA in 2020.

On January 16, 2023 Bavarian Nordic A/S (OMX: BAVA) reported preliminary, unaudited financial results for 2022, exceeding the financial guidance for the year (Press release, Bavarian Nordic, JAN 16, 2023, View Source [SID1234626266]). During 2022, the Company upgraded its financial guidance seven times. The results reported today are compared to the latest guidance, which was issued on September 7, 2022. For comparison with original guidance, see table below.

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Revenue for the full year was approximately DKK 3,151 million, compared to guided revenue in the interval of DKK 2,800 to 3,000 million. Revenue was comprised of:
DKK 1,730 million from sale of JYNNEOS/IMVANEX/IMVAMUNE mpox/smallpox vaccine
DKK 879 million from sale of Rabipur/RabAvert
DKK 299 million from sale Encepur
DKK 79 million from sale of third-party products
DKK 164 million in other income
The operating result (EBITDA) was a profit of approximately DKK 329 million, compared to a guided loss in the interval DKK -200 to 0 million.

Cash and cash equivalents at year-end was DKK 1,742 million, compared to a guided amount of DKK >1,700 million. The guidance assumed a bank debt level at year-end of DKK 600 million, however remaining bank debt was repaid during the fourth quarter.

The improved revenue is largely resulting from shipment of more mpox vaccines than anticipated in the latest guidance, which reflected some uncertainty related to the timing of deliveries and invoicing towards the end of 2022. Also, a continued strong performance in the rabies business has contributed to the improvement. Combined with a general cost-conscious approach, the operating result has been significantly improved, and Bavarian Nordic will now deliver profitability on EBITDA for 2022.

"Compared to our original guidance for 2022, we have nearly tripled our revenues and have turned profitable in a year that was otherwise expected to draw on our cash resources as we embarked on two large Phase 3 trials which have driven significant R&D costs. It has been a remarkable year and we are very pleased to announce these results, which primarily have been made possible due to the significant order flow for our mpox vaccine during the year, and it is highly encouraging that we have been able to advance our promising late-stage pipeline and still deliver such a strong financial result for the year," said Paul Chaplin, President and CEO of Bavarian Nordic.

The consolidated, audited financial results for 2022 will become available on March 2, 2023, in connection with publication of the Company’s annual report for 2022.

DKK million

Numbers are approximate

FY 2022 guidance
original, 04-Mar-2022

FY 2022 guidance

latest, 07-Sep-2022

FY 2022 preliminary

unaudited

Revenue

1,100 – 1,400

2,800 – 3,000

3,151

EBITDA

(1,300) – (1,000)

(200) – 0

329

Cash and cash equivalents

1,000 – 1,200*

> 1,700*

1,742*

* Guidance assumed a bank debt level of DKK 600 million whereas actual year-end cash position includes no bank debt, as this was repaid during fourth quarter.

On January 16, 2023 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, reported that the first patient has been treated in a Phase 1 first-in-human study evaluating the safety, tolerability, and efficacy of MP0533, the company’s candidate for acute myeloid leukemia (AML) (Press release, Molecular Partners, JAN 16, 2023, View Source [SID1234626265]). MP0533 is designed to focus an immune attack against AML in a new way that preferentially spares healthy cells, which has been a historic challenge for CD3-targeting therapeutics.

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"AML is a notoriously difficult cancer to treat, largely due to the overlapping targets expressed on both healthy and leukemic cells. Our team has worked relentlessly over the past three years to develop a molecule intended to target these cancerous cells while avoiding healthy cells. MP0533’s mechanism represents a new level of precision targeting in complex cancers that may permit greater use of the cytotoxic power of engaging CD3," said Nicolas Leupin, M.D., Ph.D., Chief Medical Officer of Molecular Partners. "We are grateful to our team and our collaborators for reaching this milestone and look forward to learning more about the potential of MP0533 to help these patients."

MP0533 simultaneously targets three surface proteins, CD33, CD123, and CD70, that are vastly more likely to be expressed together on AML blast cells and leukemic stem cells over healthy cells. It also targets CD3 on cytotoxic T cells, which will preferentially activate when at least two of the surface proteins are bound. This novel mechanism is intended to greatly favor CD3 activation in leukemic stem cells rather than the systemic activation seen in previous CD3-based T cell engagers.

The Phase 1 open-label dose escalation study will enroll patients with relapsed/refractory AML and higher-risk myelodysplastic syndromes (MDS). It is designed to assess the safety, tolerability, and efficacy of MP0533 in addition to a range of secondary endpoints, such as the effect on LSCs, pharmacokinetics, T-cell activation, and cytokine release. Between 20-45 patients are expected to be enrolled across five sites in Switzerland and the Netherlands in collaboration with select sites within the HOVON cooperative group. Additional clinical sites are planned as well.

MP0533 preclinical data demonstrates it induces preferential T cell mediated killing of cells expressing two or three of the tumor associated antigens (TAAs) compared to cells expressing a single TAA. MP0533 also demonstrated an ability to induce T cell activation and killing of AML cells in samples from newly diagnosed and previously treated patients. The research also showed that MP0533 was able to directly target and kill LSCs while sparing a variety of healthy cells including hematopoietic stem cells, endothelial cells, and T cells.