On March 23, 2023 Pionyr Immunotherapeutics, Inc., a company developing first-in-class Myeloid TuningTM antibody therapeutics that enhance the body’s anti-tumor immunity by altering, or "tuning," immune cells within the tumor microenvironment, reported that Pionyr and Gilead Sciences, Inc. (Nasdaq: GILD) have mutually agreed to change their 2020 exclusive option agreements. Gilead has waived its exclusive option to acquire Pionyr and certain other rights under the 2020 agreements (Press release, Pionyr Immunotherapeutics, MAR 23, 2023, View Source [SID1234629270]). Gilead will retain its 49% equity stake in Pionyr as well as its right, under certain conditions, to review new data as it emerges. Pionyr is now free to pursue fundraising and partnering opportunities as part of its ongoing strategy.

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"We’ve made significant progress with our Myeloid Tuning platform and our clinical stage pipeline, and we are in a strong position to reach multiple inflection points for all of our programs in the next 12 to 18 months"

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"We’ve made significant progress with our Myeloid Tuning platform and our clinical stage pipeline, and we are in a strong position to reach multiple inflection points for all of our programs in the next 12 to 18 months," noted Steven P. James, Chief Executive Officer of Pionyr. "We have appreciated the collaboration with Gilead over the last two and a half years, and their support has put us in a strong position to continue our mission of dramatically improving the treatment of cancer."

Pionyr is continuing Phase 1b development of two monoclonal antibody drugs targeting TREM1 and TREM2 and is poised to file an IND this year for a third program targeting MARCO. TREM2, TREM1 and MARCO represent novel targets present on distinct populations of myeloid cells in the tumor microenvironment associated with suppression of the immune response to multiple tumor types. In Phase 1a and 1b studies, PY314 and PY159 have demonstrated encouraging safety and tolerability both alone and in combination with pembrolizumab warranting further clinical investigation. PY314, PY159 and PY265 are first-in-class assets that target these cellular populations to enhance anti-tumor immunity.

In 2020, Gilead paid $275 million for its equity stake in Pionyr and agreed to fund Pionyr’s clinical and research activities in exchange for an exclusive option to acquire Pionyr for a pre-set price and contingent payments. As part of this agreement, Gilead waives its exclusive option to acquire Pionyr. Pionyr will be responsible for ongoing development of its pipeline, which includes PY159, PY314 and PY265. The company has the resources to advance its pipeline for the next two years. Within that timeframe, Pionyr will continue enrollment in Phase 1b expansion cohorts for both PY159 and PY314 in the refractory setting and is planning to add new frontline cohorts for both candidates. Pionyr has also completed IND-enabling studies for PY265 and will be ready to file an IND for that program in 2023.

About Myeloid TuningTM

Pionyr has developed a therapeutic platform called Myeloid TuningTM, a process that rebalances the tumor microenvironment (TME) to promote anti-tumor immunity. Myeloid cells are a type of immune cell and are part of a family of cell types that regulate both the activation and suppression of the immune response to cancer.

One such critical type of myeloid cell, tumor-associated macrophages (TAMs), are a key component of the TME. TAMs are generally categorized into two functionally contrasting subtypes, called M1-like and M2-like macrophages. M1-like macrophages are inflammatory and have anti-tumor functions, including directly mediating antibody-dependent cell-mediated cytotoxicity (ADCC) to kill tumor cells.

Alternatively, M2-like macrophages are immune suppressive, and thereby inhibit T-cell-mediated anti-tumor responses, allowing for tumor angiogenesis, growth, and progression.

Myeloid Tuning describes the process of introducing agents that shift the balance of inhibitory myeloid cells—including M2-like TAMs—toward a more inflammatory, M1-like phenotype, to promote anti-tumor immune responses in the TME that destroy solid tumors.

On March 23, 2023 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported its consolidated financial results1 for the year ending December 31, 2022 (Press release, Innate Pharma, MAR 23, 2023, View Source [SID1234629269]). The consolidated financial statements are attached to this press release.

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"In 2022 we made important progress in our pipeline, both on our clinical and preclinical projects as well as maintaining a strong financial position. We’re continuing to see encouraging efficacy signals for our proprietary program lacutamab in advanced cutaneous T cell lymphomas. In the meantime, our innovative R&D pipeline progression was marked by the expansion of our partnership with Sanofi to develop new NK Cell Engager Therapeutics from our ANKET platform, including solid tumors. The Sanofi collaboration is an example of how we use partnerships to build value at Innate, also underlined by our partnership with AstraZeneca for monalizumab which is in a Phase 3 trial for non-small cell lung cancer," said Mondher Mahjoubi, Chief Executive Officer of Innate Pharma. "As we look to progress our pipeline in house or with partnerships, we look forward to new milestones in 2023 with important inflection points, including final readouts from the TELLOMAK Phase 2 trial with lacutamab and further updates for our ANKET assets."

Webcast and conference call will be held today at 2:00pm CET (9:00am EDT)

Access to live webcast:

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Participants may also join via telephone using the registration link below:

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This information can also be found on the Investors section of the Innate Pharma website, www.innate-pharma.com.

A replay of the webcast will be available on the Company website for 90 days following the event.

1 This press release contains financial data approved by the Executive Board based on our consolidated financial statements for the year ended December 31, 2022. The audit is in progress at the date of this communication.

2 Including short term investments (€17.3m) and non-current financial instruments (€35.1m).

Pipeline highlights:

Lacutamab (IPH4102, anti-KIR3DL2 antibody):

Innate continues to see progress for lacutamab with final data from the TELLOMAK Phase 2 trial for both mycosis fungoides and Sézary syndrome expected in H2 2023.
In preliminary results confirming clinical activity and a favorable safety profile in patients with mycosis fungoides (MF) who were previously treated with at least two lines of systemic therapy, lacutamab produced a global objective response rate (ORR) of 28.6% (95% confidence interval [CI]: 13.8-50.0) in the KIR3DL2-expressing MF patients (n=21), including 2 complete responses and 4 partial responses (EORTC-CLTG (European Organisation for Research and Treatment of Cancer – Cutaneous Lymphoma Tumours Group) 2022 meeting – September 2022).
In a preliminary analysis, lacutamab demonstrated clinical activity and a favorable safety profile in heavily pretreated, post-mogamulizumab patients with advanced Sézary syndrome. In the Intention To Treat (ITT) population (n=37), the global ORR was 21.6% (8/37). ORR in the blood was 37.8% (95% CI: 24.1-53.9), with 21.6% (8/37) achieving complete response (CR). ORR in the skin was 35.1% (95% CI: 21.8-51.2). In the Evaluable for Efficacy (EES) population (n=35), global objective response rate (ORR) was 22.9% (8/35). ORR in the blood was 40.0% (95% CI: 25.6-56.4) and ORR in the skin was 37.1% (95% CI: 23.2 53.7) (2022 ASH (Free ASH Whitepaper) (American Society Hematology) Annual Meeting – December 2022).
Two parallel clinical trials to study lacutamab in patients with KIR3DL2-expressing, relapsed/refractory peripheral T-cell lymphoma (PTCL) are ongoing. Initial PTCL data are expected in H2 2023.
Phase 1b trial: a Company-sponsored Phase 1b clinical trial to evaluate lacutamab as a monotherapy in patients with KIR3DL2-expressing relapsed PTCL. A poster on the trial design was presented at the ESMO (Free ESMO Whitepaper) (European Society for Medical Oncology) 2022 conference.
Phase 2 KILT (anti-KIR in T Cell Lymphoma) trial: The Lymphoma Study Association (LYSA) initiated an investigator-sponsored, randomized trial to evaluate lacutamab in combination with chemotherapy GEMOX (gemcitabine in combination with oxaliplatin) versus GEMOX alone in patients with KIR3DL2-expressing relapsed/refractory PTCL.
ANKET (Antibody-based NK cell Engager Therapeutics):

ANKET is Innate’s proprietary platform for developing next-generation, multi-specific NK cell engagers to treat certain types of cancer. Innate’s pipeline includes four public drug candidates born from the ANKET platform: IPH6101 (CD123-targeted), IPH6401 (BCMA-targeted), IPH62 (B7-H3-targeted) and tetra-specific IPH6501 (CD20-targeted). Several other undisclosed proprietary preclinical targets are being explored.

IPH6101, IPH6401 and IPH62 (partnered with Sanofi)

The Phase 1/2 clinical trial by Sanofi is progressing well, evaluating IPH6101/SAR’579, the first NKp46/CD16-based CD123-targeted ANKET platform NK cell engager, in patients with relapsed or refractory acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia or high-risk myelodysplastic syndrome.
Preclinical data showing the control of AML cells by a trifunctional NKp46-CD16a-NK cell engager targeting CD123 were published in Nature Biotechnology in January 2023.
On July 21, 2022, the Company announced that its partner Sanofi had made the decision to progress IPH6401/SAR’514, a BCMA-targeting NK cell engager into investigational new drug (IND)-enabling studies. Selection of IPH6401/SAR’514 triggered a €3M milestone payment to Innate.
As announced on December 19, 2022, Sanofi licensed IPH62, a NK cell engager program targeting B7-H3 from Innate’s ANKET platform. Sanofi also have the option to add up to two additional ANKET targets. Upon candidate selection, Sanofi will be responsible for all development, manufacturing and commercialization. Under the terms of the agreement, Innate received a €25m upfront payment and is eligible for up to €1.35bn total in preclinical, clinical, regulatory and commercial milestones plus royalties on potential net sales.
IPH6501 (proprietary)

Progress continues toward a Phase 1 clinical trial in 2023 for the proprietary CD20 targeted tetra-specific ANKET, IPH6501.
An October 2022 edition of Cell Reports Medicine described the development of Innate’s fit-for-purpose ANKET antibody-based tetra-specific molecule to harness the antitumor functions of NK cells, boosting their capacity to proliferate, to accumulate at the tumor site and to kill tumor cells.
Monalizumab (anti-NKG2A antibody), partnered with AstraZeneca:

Innate continues to see progress for monalizumab in the early non-small cell lung cancer (NSCLC) setting, with the ongoing Phase 3 PACIFIC-9 study run by AstraZeneca. The study is evaluating durvalumab (anti-PD-L1) in combination with monalizumab or AstraZeneca’s oleclumab (anti-CD73) in patients with unresectable, Stage III NSCLC who have not progressed following definitive platinum-based concurrent chemoradiation therapy (CRT).
On April 29, 2022, Innate announced a $50 million milestone payment from AstraZeneca was triggered for dosing the first patient in the PACIFIC-9 Phase 3 clinical trial.
Detailed results from the randomized AstraZeneca-sponsored Phase 2 COAST clinical trial, including monalizumab data in combination with durvalumab, were published in the Journal of Clinical Oncology in April 2022. The results were initially presented during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021. The results of the interim analysis showed monalizumab in combination with durvalumab reduced the risk of disease progression by 58% (improved progression-free survival (PFS) with a hazard ratio of 0.42) and improved objective response rate (ORR) compared to durvalumab alone in patients with unresectable, Stage III NSCLC who had not progressed after concurrent CRT. The Journal of Clinical Oncology publication includes exploratory subgroup analysis.
Partner AstraZeneca presented data from Phase 2 NeoCOAST randomized trial in resectable, early-stage NSCLC at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting and ESMO (Free ESMO Whitepaper) 2022 congress. The presentations highlighted improved disease responses with durvalumab in combination with monalizumab, oleclumab or danvatirsen, when compared to durvalumab alone. The follow-up randomized Phase 2 clinical trial, NeoCOAST-2, is enrolling patients with resectable, stage IIA-IIIB NSCLC to receive neoadjuvant durvalumab combined with chemotherapy and either oleclumab or monalizumab, followed by surgery and adjuvant durvalumab plus oleclumab or monalizumab.
On August 1, 2022, Innate announced that a planned futility interim analysis of the Phase 3 INTERLINK-1 study sponsored by AstraZeneca did not meet a pre-defined threshold for efficacy. The Company announced that, based on the result and the recommendation of an Independent Data Monitoring Committee, the study was to be discontinued. There were no new safety findings. AstraZeneca plan to share the data in due course. The INTERLINK-1 study evaluated monalizumab in combination with cetuximab vs. cetuximab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck who have been previously treated with platinum-based chemotherapy and PD-(L)1 inhibitors.
IPH5201 (anti-CD39), partnered with AstraZeneca:

The MATISSE Phase 2 clinical trial conducted by Innate in neoadjuvant lung cancer for IPH5201, an anti-CD39 blocking monoclonal antibody developed in collaboration with AstraZeneca, has started and is awaiting first patient dosed.
In August 2022 Innate received a $5 million milestone payment from AstraZeneca and will be responsible for conducting the study. AstraZeneca and Innate will share study costs and AstraZeneca will supply clinical trial drugs.
Preclinical data supporting the rationale for the Phase 2 development in NSCLC were presented at the 2022 ESMO (Free ESMO Whitepaper) Immuno-Oncology (IO) Annual Congress in December.
AstraZeneca conducted a Phase 1 trial in solid tumors with IPH5201 alone or in combination with durvalumab and presented a poster entitled "IPH5201 as Monotherapy or in Combination with Durvalumab in Advanced Solid Tumours" at the 2022 ESMO (Free ESMO Whitepaper) IO Annual Congress in December.
IPH5301 (anti-CD73):

The investigator-sponsored CHANCES Phase 1 trial of IPH5301, in collaboration with Institut Paoli-Calmettes is ongoing. The trial will be conducted in two parts, Part 1, the dose escalation, followed by a Part 2 safety expansion study cohort. Part 2 will evaluate IPH5301 in combination with chemotherapy and trastuzumab in HER2+ cancer patients. The design of the Phase 1 study was highlighted at the 2022 ESMO (Free ESMO Whitepaper) IO congress in December.
Avdoralimab (anti-C5aR1):

The Company has decided to discontinue the development of avdoralimab in bullous pemphigoid. The Company will continue to evaluate out-licensing as a potential next step.
Preclinical assets:

Fueling the R&D engine, the Company continues to develop different approaches for the treatment of cancer utilizing its antibody engineering capabilities to deliver novel assets, with its innovative ANKET platform and continuing to explore Antibody Drug Conjugates (ADC) formats.
During the period, the Company received from AstraZeneca a notice that it will not exercise its option to license the four preclinical programs covered in the "Future Programs Option Agreement". This option agreement was part 2018 multi-term agreement between AstraZeneca and Innate. Innate regained full rights to further develop the four preclinical molecules.
Corporate Update:

On May 3, 2022 Innate announced the commencement of an At-The-Market (ATM) program, pursuant to which it may, from time to time, offer and sell to eligible investors a total gross amount of up to $75 million American Depositary Shares ("ADS"). Each ADS representing one ordinary share of Innate. As of December 31, 2022, the balance available under our May 2022 sales agreement remains at $75 million.
Dr Sally Bennett was appointed as new member of the Supervisory Board in May 2022. She was appointed as a member of the Audit Committee. On the same date it was announced that Mr Patrick Langlois decided to resign from his mandate of Supervisory Board member of Innate Pharma.
In January 2023, Mrs Claire de Saint Blanquat, Vice President Legal and Corporate Affairs, and Mr Henry Wheeler, Vice President Investor Relations and Communications, were appointed to the Leadership Team.
Financial highlights for 2022:

The key elements of Innate’s financial position and financial results as of and for the year ended December 31, 2022 are as follows:

Cash, cash equivalents, short-term investments and financial assets amounting to €136.6 million (€m) as of December 31, 2022 (€159.7m as of December 31, 2021), including financial instruments amounting to €35.1m (€39.9m as of December 31, 2021). Cash, cash equivalents as of December 31, 2022 do not include the €25.0 million payment received from Sanofi in March 2023.
As of December 31, 2022, financial liabilities amount to €42.3m (€44.3m as of December 31, 2021). In August 2022, the Company obtained an extension for a period of five year (starting in 2022) with a one-year grace period (2023) of its State-Guaranted Loans (Prêts Garantis par l’Etat "PGE") from Société Générale (€20.0m) and BNP Paribas (€8.7m).
Revenue and other income from continuing operations amounted to €57.7m in 2022 (2021: €24.7m). It mainly comprises revenue from collaboration and licensing agreements (€49.6m in 2022 vs €12.1m in 2021), and research tax credit (€7.9m in 2022 vs €10.3m in 2021, -23.1%):
Revenue from collaboration and licensing agreements, which mainly resulted from the partial or entire recognition of the proceeds received pursuant to the agreements with AstraZeneca and Sanofi and which are recognized on the basis of the percentage of completion of the works performed by the Company under such agreements:
(i) Revenue from collaboration and licensing agreements for monalizumab increased by €14.9m to €22.4m in 2022 (€7.5m in 2021). This change mainly results from the transaction price increase of €13.4m ($14.0m) triggered by the launch of the "PACIFIC-9" Phase 3 trial announced on April 29, 2022. This change in the transaction price generated a €12.6 million favorable cumulative adjustment in the revenue related to monalizumab agreements for the first half of 2022, partially offset by effects of the decrease in direct monalizumab research and development costs over the period as compared to the first half of 2021, in connection with the Phase 1 & 2 trials maturity;
(ii) Revenue related to IPH5201 for the year ended 2022 amounted to €4.7m and results from the entire recognition in revenue of the $5.0m milestone payment received in August 2022 from AstraZeneca following the signature on June 1, 2022 of an amendment to the initial contract signed in October 2018. This amendment sets the terms of the collaboration following AstraZeneca’s decision to advance IPH5201 to a Phase 2 study;
(iii) During 2022 first semester, the Company received from AstraZeneca a notice that it will not exercise its option to license the four preclinical programs covered in the "Future Programs Option Agreement". This option agreement was part of the 2018 multi-term agreement between AstraZeneca and the Company under which the Company received an upfront payment of $20.0m (€17.4m). Innate has now regained full rights to further develop the four preclinical molecules. Consequently, the entire initial payment of $20.0m, or €17.4m was recognized as revenue in 2022.
(iv) During 2022 first semester, the Company was informed of Sanofi’s decision to advance IPH6401/SAR’514 into investigational new drug (IND)-enabling studies. As such, Sanofi has selected a second multispecific antibody engaging NK cells as a drug candidate. This selection triggered a €3.0m milestone payment from Sanofi. This amount was received by the Company on September 9, 2022.
The variation in the research tax credit mainly results from a decrease in the amortization for the intangible assets related to acquired licenses (monalizumab and IPH5201) and to the decrease in personnel expenses allocated to research and development operations. In addition, there was a decrease in public subcontracting included in the calculation of the CIR. This decrease is the consequence of the end of the doubling of public subcontracting expenses eligible for the CIR since January 1, 2022, partly offset by an increase in private subcontracting expenses with accredited suppliers.
Operating expenses from continuing operations amounted to €74.1m in 2022 (2021: €72.5m, +2.2%):
General and administrative (G&A) expenses from continuing activities amounted to €22.4m in 2022 (2021: €25.5m, -12.1%). This variation results cumulatively from (i) a decrease in wages mainly resulting from restructuring costs and higher annual bonuses level in 2021, (ii) a decrease in non-scientific advisory fees and (iii) a decrease in other general and administrative expenses.
Research and development (R&D) expenses from continuing activities amounted to €51.7m in 2022 (2021: €47.0m, 9.9%). This variation mainly results from (i) an increase in direct research and development expenses (clinical and non-clinical) and (ii) an increase in other indirect research and development expenses, mainly linked to non-scientific and scientific fees.
The avdoralimab intangible asset (anti-C5aR rights) total impairment of €41.0m (non-cash expense) following the Company’s decision to stop avdoralimab development in bullous pemphigoid indication in inflammation.
A net financial income of €0.5m in 2022 (2021: €2.3m gain).
A net loss from Lumoxiti discontinued operations of €0.1m in 2022 (2021: net loss of €7.3m, -98.2%). This decrease mainly resulted from the Settlement Amount of $6.2m (€5.5m as of December 31, 2021) paid to AstraZeneca in April 2022 for an amount of €5.9m under the Termination and Transition agreement.
A net loss of €58.1m in 2022 (2021: net loss of €52.8m).
The table below summarizes the IFRS consolidated financial statements as of and for the year ended December 31, 2022, including 2021 comparative information.

In thousands of euros, except for data per share

December 31, 2022

December 31, 2021

Revenue and other income

57,674

24,703

Research and development

(51,663)

(47,004)

Selling, general and administrative

(22,436)

(25,524)

Total operating expenses

(74,099)

(72,528)

Operating income (loss) before impairment

(16,425)

(47,825)

Impairment of intangible asset

(41,000)

—

Operating income (loss) after impairment

(57,425)

(47,825)

Net financial income (loss)

(546)

2,347

Income tax expense

—

—

Net income (loss) from continuing operations

(57,972)

(45,478)

Net income (loss) from discontinued operations

(131)

(7,331)

Net income (loss)

(58,103)

(52,809)

Weighted average number of shares outstanding (in thousands)

79,640

79,543

Basic income (loss) per share

(0.73)

(0.66)

Diluted income (loss) per share

(0.73)

(0.66)

Basic income (loss) per share from continuing operations

(0.73)

(0.57)

Diluted income (loss) per share from continuing operations

(0.73)

(0.57)

Basic income (loss) per share from discontinued operations

—

(0.09)

Diluted income (loss) per share from discontinued operations

—

(0.09)

December 31, 2022

December 31, 2021

Cash, cash equivalents and financial asset

136,604

159,714

Total assets

207,863

267,496

Shareholders’ equity

54,151

107,440

Total financial debt

42,251

44,251

On March 23, 2023 ONO PHARMA USA, INC., reported that its candidate, tirabrutinib (ONO-4059), a Bruton’s tyrosine kinase inhibitor, was granted Orphan Drug Designation on March 21, 2023 by the U.S. Food and Drug Administration (FDA) for the treatment of patients with primary central nervous system lymphoma (PCNSL) (Press release, Ono Pharmaceutical Co, MAR 23, 2023, View Source [SID1234629268]).

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The FDA’s Orphan Drug Designation program supports the development and evaluation of investigational drugs and biologics that show promise for the diagnosis, treatment, or prevention of rare diseases or disorders, affecting fewer than 200,000 people in the United States (U.S.).

PCNSL is a rare and aggressive extra nodal non-Hodgkin lymphoma affecting the brain, its protective membranes, the spinal cord, and/or eye, without systemic involvement at the time of diagnosis. In the U.S., the incidence of PCNSL is approximately five out of 1,000,000 people per year, with higher rates in people over 65 years old.1 Symptoms can vary depending on the location of the tumor and may include headache, nausea, vomiting, visual symptoms, and seizures, among others. ONO is currently recruiting newly diagnosed and relapsed or refractory adult PCNSL patients in the U.S. for the PROSPECT clinical study (www.theprospectstudy.com; NCT04947319).

"We are extremely pleased that tirabrutinib has been granted orphan drug status for the treatment of PCNSL," said Kunihiko Ito, President and CEO of ONO PHARMA USA. "The designation represents a milestone for ONO. Currently, ONO is carrying out a Phase 2 trial of tirabrutinib in people with newly diagnosed or relapsed/refractory PCNSL, and we look forward to advancing clinical trials so that patients may have therapeutic options as soon as possible."

About PCNSL
PCNSL is a rare and aggressive extra nodal non-Hodgkin lymphoma (NHL) that is confined to the brain parenchyma, spinal cord, eye, or leptomeninges, without systemic involvement. The annual incidence rate of PCNSL is approximately five cases per 1,000,000 people in the U.S. The rate can further increase among immunocompetent people aged 65 years and older. The signs and symptoms presented in patients with PCNSL vary depending on the neuroanatomical site of the lesion, and include cranial neuropathy, neuropsychiatric symptoms, symptoms associated with increased intracranial pressure, seizures, ocular symptoms, headache, dysmotility, cranial neuropathy, and radiculopathy. There are no therapeutic products specifically approved for the treatment of PCNSL in the U.S., and data guiding therapeutic approaches are very limited. Despite recent progress resulting in the improvement of clinical outcomes in newly diagnosed patients with PCNSL after an induction treatment, approximately 20 to 30 percent of patients are refractory to the initial treatment, and up to 60 percent of patients will eventually relapse.

About Tirabrutinib
Tirabrutinib, discovered and developed by Ono Pharmaceutical Co., Ltd., is a highly potent selective BTK inhibitor. Signaling through the B-cell receptor (BCR) regulates cellular proliferation and activation, and promotes survival, differentiation, and clonal expansion of B-cells. The BCR signaling pathway plays an important role in a number of B-cell malignancies. Gene expression profiling data revealed BCR signaling as the most prominent pathway activated in chronic lymphocytic leukemia (CLL) cells isolated from lymphatic tissues. In Japan, tirabrutinib was approved in March 2020 for the treatment of relapsed or refractory PCNSL and launched under the tradename of Velexbru in May 2020. In addition, tirabrutinib was approved for the treatment of relapsed or refractory PCNSL in South Korea in November 2021 and in Taiwan in February 2022. Moreover, Velexbru was approved for the treatment of Waldenstrom macroglobulinemia and lymphoplasmacytic lymphoma in Japan in August 2020.

About the PROSPECT Study
The PROSPECT Study is the Phase 2 trial (NCT04947319) evaluating the safety and effectiveness of an investigational oral medicine called tirabrutinib for potential treatment of newly diagnosed or relapsed/refractory primary central nervous system lymphoma, which is a type of cancer that either does not improve from treatment (refractory) or improves only for a limited time (relapsed). Current treatment options for relapsed or refractory PCNSL are limited, and there are no medications approved in the U.S. for the treatment of PCNSL. Learn more about the PROSPECT Study here: www.theprospectstudy.com.

On March 23, 2023 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported an upcoming poster presentation for the ongoing Phase 1/2 ALKOVE-1 study of its ALK-selective inhibitor, NVL-655 (Press release, Nuvalent, MAR 23, 2023, View Source [SID1234629267]). The poster will be presented at the European Lung Cancer Congress (ELCC 2023), taking place in Copenhagen, Denmark, and virtually, March 29 – April 1, 2023.

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The "Trial in Progress" poster includes background and study design considerations for the ALKOVE-1 Phase 1/2 study (NCT05384626) evaluating the safety and preliminary activity of NVL-655 in patients with solid tumors harboring oncogenic ALK alterations, including those with acquired ALK resistance mutations and CNS metastases. The first-in-human, multicenter, open-label, dose-escalation and expansion study is currently evaluating NVL-655 as an oral monotherapy in the Phase 1 portion.

The poster will be archived on the Nuvalent website at www.nuvalent.com following the presentation.

Details for the poster presentation are as follows:

Title: NVL-655, a Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor, in Patients with Advanced ALK-Positive Solid Tumors: The Phase 1/2 ALKOVE-1 Study
Authors: Melissa Johnson1, Sai-Hong Ignatius Ou2, Enriqueta Felip3, Christina Baik4, Benjamin Besse5, Julien Mazieres6, D. Ross Camidge7, Shirish Gadgeel8, Alexander Drilon9, Yasir Elamin10, Geoffrey Liu11, Joshua E. Reuss12, Tina Kehrig13, Henry E. Pelish13, Viola Zhu13, Jessica J. Lin14
Presentation Number: 81TiP
Abstract Category: Advanced NSCLC
Session Date and Time: Friday, March 31, 2023 from 12:00 – 12:45pm CEST
Location: Bella Center Copenhagen, Exhibition and Poster Area

1Sarah Cannon Research Institute, Nashville, TN, United States of America, 2University of California Irvine Medical Center, Orange, CA, United States of America, 3Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, Barcelona, Spain, 4Fred Hutchinson Cancer Center, Seattle, WA, United States of America, 5Institut Gustave Roussy, Villejuif, France, 6Institut Universitaire du Cancer, Toulouse, France, 7University of Colorado Cancer Center – Anschutz Medical Campus, Aurora, CO, United States of America, 8Henry Ford Cancer Institute, Detroit, MI, United States of America, 9Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York, NY, United States of America, 10MD Anderson Cancer Center, Houston, TX, United States of America, 11Princess Margaret Cancer Center, Toronto, Ontario, Canada, 12Georgetown University, Washington, DC, United States of America, 13Nuvalent, Inc., Cambridge, MA, United States of America, 14Massachusetts General Hospital, Boston, MA, United States of America

About NVL-655

NVL-655 is a novel brain-penetrant ALK-selective inhibitor created to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with the solvent front G1202R mutation or compound mutations G1202R / L1196M ("GRLM"), G1202R / G1269A ("GRGA"), or G1202R/L1198F ("GRLF"). NVL-655 has been optimized for CNS penetrance to improve treatment options for patients with brain metastases. NVL-655 has been observed in preclinical studies to selectively inhibit wild-type ALK and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and drive more durable responses for patients. NVL-655 is currently being investigated in the ALKOVE-1 study (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors.

On March 23, 2023 Shanghai Henlius Biotech, Inc. (2696.HK) reported that the European Medicines Agency (EMA) has validated the application for its self-developed anti-PD-1 monoclonal antibody (mAb) HANSIZHUANG (serplulimab), in combination with chemotherapy (carboplatin and etoposide), for the first-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC) (Press release, Shanghai Henlius Biotech, MAR 23, 2023, View Source [SID1234629266]). The European Commission (EC) previously granted Orphan Drug Designation (ODD) to HANSIZHUANG for the treatment of small cell lung cancer (SCLC).

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"HANSIZHUANG is Henlius’ first innovative mAb, as well as the first and only anti-PD-1 therapy approved for treatment of SCLC, which has benefited 13,000 SCLC patients in China. Since launched in March 2022, it has been approved for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer and ES-SCLC in China," said Jason Zhu, President of Henlius. "HANSIZHUANG is steadily making its way from China to Europe and the U.S. Previously, we had Zercepac approved in more than 30 countries including the European Union. We hope HANSIZHUANG will further open that market and spur global expansion as we seek to benefit more patients."

Enhance the global presence

The regulatory application is based on data from ASTRUM-005, a randomized, double-blind, placebo-controlled international multi-centre phase 3 clinical study, which evaluated the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with ES-SCLC. The study has set up a total of 128 sites in various countries including China, Poland, Turkey, and Georgia, and enrolled 585 subjects, among whom 31.5% were White. The results of ASTRUM-005 were presented in oral for the first time at the 2022 ASCO (Free ASCO Whitepaper) annual meeting and was then published in the Journal of the American Medical Association (JAMA, impact factor of 157.3), one of the top four medical journals in the world, which made ASTRUM-005 the first study published on JAMA in SCLC immunotherapy, demonstrating the high level of academic acclaim on a global scale.

In 2022, HANSIZHUANG was also granted ODD by the Food and Drug Administration (FDA) for the treatment of SCLC. The ODD granted by the FDA is beneficial for the continuous development of HANSIZHUANG and the enjoyment of certain policy support in terms of registration and commercialization in the United States (U.S.). Based on the positive feedback of FDA Biologics license Application (BLA) submission for HANSIZHUANG for the treatment of ES-SCLC and the discussion results of the FDA’s Class C consultation meeting, Henlius has initiated a bridging head-to-head trial in U.S. patients with ES-SCLC to evaluate the efficacy of HANSIZHUANG, which propels the product towards U.S. market approval further.

More are on the horizon

HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius and has since seen benefits in 19,000 patients in China. Its synergy with in-house products of the company and innovative therapies are being actively promoted and 14 clinical trials on immuno-oncology combination therapies are in progress in a wide variety of indications, such as lung cancer, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. In addition to the launched indications of sqNSCLC and ES-SCLC, Henlius also explored to treat patients with non-squamous non-small cell lung cancer (nsNSCLC) and limited-stage small cell lung cancer (LS-SCLC). Recently, the first patient has been dosed in an international multi-centre phase 3 clinical trial of HANSIZHUANG (serplulimab) in patients with LS-SCLC in the U.S. In the field of gastrointestinal cancer, HANSIZHUANG has been approved for the treatment of MSI-H solid tumours, which could benefit patients with MSI-H colorectal cancer and MSI-H gastric cancer. It was also recommended for the first-line treatment of esophageal cancer (category IA) in the 2022 China Guidelines for Radiotherapy of Esophageal Cancer and its NDA for the first-line treatment of esophageal squamous cell carcinoma (ESCC) was accepted by the NMPA based on the data of ASTRUM-007, which was published in Nature Medicine (IF: 87.241). In addition, PD-1 inhibitors are less explored in neoadjuvant/adjuvant therapies for gastric cancer, and Henlius has led the way with a phase 3 clinical study, striving to benefit gastric cancer patients from the early line of immunotherapy.

Through overseas development of HANSIZHUANG, Henlius will accelerate the pace of global internationalisation and deliver more high-quality, affordable treatment options to patients.

About HANSIZHUANG

HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first anti-PD-1 mAb for the first-line treatment of SCLC. Up to date, 3 indications are approved for marketing in China, 2 marketing applications are under review in China and the EU, and more than 10 clinical trials are ongoing across the world.

HANSIZHUANG was launched in March 2022 and has been approved by the NMPA for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC). The marketing applications of the first-line treatment for esophageal squamous cell carcinoma (ESCC) and ES-SCLC are under review by the NMPA and the EMA, respectively. Focus on lung and gastrointestinal cancer, the synergy of HANSIZHUANG with in-house products of the company and innovative therapies are being actively promoted. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 14 clinical trials on immuno-oncology combination therapies in a wide variety of indications. As of now, the company has enrolled more than 3,500 subjects in China, the U.S., Turkey, Poland, Georgia and other countries and regions, and the proportion of White is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The results of 3 pivotal trials of HANSIZHUANG were published in the Journal of the American Medical Association (JAMA, IF: 157.3), Nature Medicine (IF: 87.241), and the British Journal of Cancer (IF: 9.075), respectively. Furthermore, HANSIZHUANG was respectively recommended for the first-line treatment of ES-SCLC in the 2022 CSCO Guidelines for Diagnosis and Treatment of Small Cell Lung Cancer (SCLC) and the treatment of esophageal cancer (category IA) in the 2022 China Guidelines for Radiotherapy of Esophageal Cancer. Serplulimab was also granted orphan drug designations by the FDA and the EC for the treatment of SCLC, and the first patient has been dosed in a bridging head-to-head trial in the United States to comparing HANSIZHUANG to standard of care Atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC.