On March 3, 2022 Helsinn Group (Helsinn), a fully integrated, global biopharma company with a diversified pipeline of innovative oncology assets and strong track-record of commercial execution, and BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio), a commercial-stage biopharmaceutical company that focuses on genetic diseases and cancers, reported an update to their existing strategic collaboration to develop, manufacture and commercialize infigratinib for oncology indications (Press release, BridgeBio, MAR 3, 2022, View Source [SID1234609476]).

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Under the terms of the amended and restated agreement, Helsinn will gain an exclusive license to commercialize infigratinib in the U.S. and will be responsible for developing, manufacturing and commercializing infigratinib in oncology indications worldwide except for achondroplasia or any other skeletal dysplasias and except in mainland China, Hong Kong and Macau. BridgeBio will be eligible to receive regulatory and commercial milestone payments as well as tiered royalties on adjusted net sales from Helsinn. BridgeBio will retain all rights to develop, manufacture and commercialize infigratinib in skeletal dysplasia, including achondroplasia.

In 2021, Helsinn and BridgeBio obtained accelerated approval for TRUSELTIQ (infigratinib) from the U.S. Food and Drug Administration (FDA) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. Additionally, the two parties received conditional approval by Health Canada and provisional approval by the Therapeutics Goods Association in Australia for TRUSELTIQ (infigratinib) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement. Continued approval in the U.S., Canada and Australia for this indication may be contingent upon confirmatory trials.

Infigratinib is not FDA-, Health Canada- or Therapeutics Goods Association-approved for any other indication in the United States, Canada and Australia, and is not approved for use by any other health authority.

Giorgio Calderari, Helsinn Group CEO commented, "We are delighted to gain the exclusive license to commercialize infigratinib in the U.S. This perfectly complements our recently announced Fully Integrated Targeted Therapy (FITT) Strategy and will utilize our unique capabilities and expertise to take products through development and to patients living with cancer across the globe. BridgeBio is a great partner, and we are looking forward to continuing our relationship with them through our non-exclusive collaboration framework to propose co-development and co-commercialization opportunities for preclinical precision oncology programs."

"We are expanding our partnership with Helsinn so that even more patients with FGFR-driven cancers will ultimately be able to access infigratinib. Focused execution means reducing the scope of our internal activity. We will continue to advance high-quality programs in our pipeline, while allowing Helsinn to develop and commercialize infigratinib in cancer indications for patients in need," said Neil Kumar, Ph.D., founder and CEO of BridgeBio.

In March 2021, Helsinn and BridgeBio entered into a global license and collaboration agreement to co-commercialize infigratinib for oncology in the U.S. and to co-develop, manufacture and commercialize infigratinib for such indications outside the U.S., excluding mainland China, Hong Kong and Macau. BridgeBio previously entered a strategic collaboration with LianBio for development and commercialization of infigratinib in oncology indications in mainland China, Hong Kong and Macau.

In November 2021, Helsinn and BridgeBio entered into a strategic collaboration to co-develop and co-commercialize a potentially first-in-class inhibitor designed to target glutathione peroxidase 4 (GPX4), which will be investigated in patients with difficult-to-treat tumors. Alongside this, Helsinn and BridgeBio established a new non-exclusive collaboration framework agreement that allows the companies to propose co-development and co-commercialization opportunities for preclinical precision oncology programs. The terms in this strategic collaboration have not changed.

About Infigratinib

Infigratinib is a potent orally administered, selective, ATP‐competitive, kinase inhibitor of FGFRs, with highest affinity for FGFR 1, 2, and 3. The therapy is currently under investigation as a potential first-line treatment for individuals with FGFR2-altered cholangiocarcinoma (bile duct cancer) and in the adjuvant setting for individuals with FGFR3-altered urothelial carcinoma (bladder cancer). Infigratinib is also in development in skeletal dysplasias for the treatment of individuals with FGFR3-altered achondroplasia. BridgeBio retains full rights to develop and commercialize infigratinib in skeletal dysplasias for the treatment of individuals with FGFR3-altered achondroplasia.

About Cholangiocarcinoma (CCA)

CCA represents an aggressive group of malignancies that form in the bile ducts. Although rare in most countries (with a worldwide estimated incidence of <6 per 100,000 people), the incidence of this malignancy is increasing worldwide. Because the disease is usually asymptomatic at early-stages, diagnosis may be delayed until advanced stages, when CCA typically presents as locally advanced or metastatic disease. Despite continuing advances in treatments, the prognosis for this disease remains poor, with a 5-year survival rate of <20%. FGFR2 genetic alterations are present in approximately 15% to 20% of CCA patients and represent potential targets for treatments.1,2

U.S. Indication and Important Safety Information for TRUSELTIQ (infigratinib)

TRUSELTIQ (infigratinib) capsules 25mg/100mg is indicated for the treatment of adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.

Accelerated approval was granted based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).

Warnings and precautions

Ocular toxicity: Retinal pigment epithelial detachment (RPED), which may cause blurred vision, occurred in 11% of 351 patients treated with TRUSELTIQ, including patients with asymptomatic RPED, with a median onset of 26 days. Perform comprehensive ophthalmological exam including optical coherence tomography prior to initiating, at 1 month, at 3 months, and then every 3 months during treatment with TRUSELTIQ. Urgently evaluate patients for onset of visual symptoms and follow up every 3 weeks until resolved or TRUSELTIQ is discontinued. Withhold TRUSELTIQ as recommended. Dry eye occurred in 29% of 351 patients; treat with ocular demulcents as needed
Hyperphosphatemia and soft tissue mineralization: Hyperphosphatemia, which can lead to soft tissue mineralization, cutaneous calcinosis, non-uremic calciphylaxis, vascular calcification, and myocardial calcification, occurred in 82% of 351 patients treated with TRUSELTIQ, with a median time to onset of 8 days (range 1-349); 83% of 351 patients treated with TRUSELTIQ received phosphate binders. Monitor for hyperphosphatemia throughout treatment. Initiate phosphate-lowering therapy for serum phosphate >5.5 mg/dL; withhold TRUSELTIQ and initiate phosphate-lowering therapy for serum phosphate >7.5 mg/dL; withhold, reduce the dose, or permanently discontinue TRUSELTIQ based on duration and severity of hyperphosphatemia
Embryo-fetal toxicity: TRUSELTIQ can cause fetal harm. Advise pregnant women of the potential risk to the fetus; advise females of reproductive potential and men who are partnered with women of reproductive potential to use effective contraception during treatment with TRUSELTIQ and for 1 month after the final dose
Adverse reactions

Most common adverse reactions (incidence ≥20%, all grades): nail toxicity, stomatitis, dry eye, fatigue, alopecia, palmar-plantar erythrodysesthesia syndrome, arthralgia, dysgeusia, constipation, abdominal pain, dry mouth, eyelash changes, diarrhea, dry skin, decreased appetite, blurred vision, and vomiting
Most common laboratory abnormalities (incidence ≥20%, all grades): increased creatinine, increased phosphate, decreased phosphate, increased alkaline phosphatase, decreased hemoglobin, increased alanine aminotransferase, increased lipase, increased calcium, decreased lymphocytes, decreased sodium, increased triglycerides, increased aspartate aminotransferase (AST), increased urate, decreased platelets, decreased leukocytes, decreased albumin, increased bilirubin, and decreased potassium
Drug interactions

CYP3A inhibitors: Avoid use with strong and moderate CYP3A inhibitors
CYP3A inducers: Avoid use with strong and moderate CYP3A inducers
Gastric acid–reducing agents: Avoid coadministration with proton pump inhibitors, histamine-2 receptor antagonists (H2RA), and locally acting antacids. If coadministration of H2RA or locally acting antacids cannot be avoided, separate TRUSELTIQ administration
H2RA: Take TRUSELTIQ 2 hours before or 10 hours after
Locally-acting antacid: Take TRUSELTIQ 2 hours before or 2 hours after
Dosage and administration

Prior to initiating TRUSELTIQ: Confirm FGFR2 fusion or rearrangement; perform comprehensive ophthalmic exam including OCT; confirm negative pregnancy test in females of reproductive potential
Starting dose: Take TRUSELTIQ orally once daily on Days 1-21 of 28-day cycles; continue treatment until disease progression or unacceptable toxicity. Take TRUSELTIQ on an empty stomach with a glass of water at least 1 hour before or 2 hours after food
No renal or hepatic impairment
125 mg (one 100 mg capsule and one 25 mg capsule)
Mild and moderate renal impairment (creatinine clearance 30-89 mL/min)
100 mg (one 100 mg capsule)
Mild hepatic impairment (total bilirubin >upper limit of normal [ULN] to 1.5 x ULN or AST > ULN)
100 mg (one 100 mg capsule)
Moderate hepatic impairment (total bilirubin >1.5 to 3 x ULN with any AST)
75 mg (three 25 mg capsules)
Dose modification: Consult the TRUSELTIQ full Prescribing Information for dose modifications and monitoring recommendations for RPED, hyperphosphatemia, and other Grades 3-4 adverse reactions
For additional information, please see the U.S. Full Prescribing Information for TRUSELTIQ

References
1Banales, J., Cardinale, V., Carpino, G. et al. Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol 13, 261–280 (2016). View Source

2 Banales, J.M., Marin, J.J.G., Lamarca, A. et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol 17, 557–588 (2020). View Source

On March 3, 2022 Median Technologies (ALMDT) reported that the company has filed a 513(g) submission on Feb. 17, 2022 to the United States Food and Drug Administration (FDA) for its iBiopsy Lung Cancer Screening (LCS) AI/ML technology-based end-to-end CADe/CADx1 Software as Medical Device (SaMD) (Press release, MEDIAN Technologies, MAR 3, 2022, View Source [SID1234609491]).

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The 513(g) submission will allow Median Technologies to determine the best product classification and choose between the De Novo or the 510(k) regulatory pathways for iBiopsy LCS CADe/CADx SaMD. The FDA is expected to review the 513(g) submission and provide feedback within 60 calendar days.

As next regulatory steps, Median Technologies is preparing several Q-submissions for Q2, 2022.

"This first regulatory submission marks the beginning of our interactions with the FDA. The FDA’s feedback will help us determine the shortest and most efficient way to bring our product onto the US healthcare market", Fredrik Brag, CEO and founder of Median Technologies said. "Lung cancer is the deadliest cancer, and being able to detect it very early is of critical importance for patients. Our innovative iBiopsy AI/ML-based technology could have a huge impact on saving patients’ lives by identifying lung cancer onsets at their earliest stage, and could significantly improve the accuracy, consistency, and adoption of lung cancer screening programs worldwide".

About iBiopsy: iBiopsy is based on the most advanced technologies in Artificial Intelligence (AI) and Data Science (DS), benefiting from Median’s expertise in medical image processing. iBiopsy targets the development of innovative AI/ML-based Software as Medical Device, to be used in several indications for which there are unmet needs regarding early diagnosis, prognosis and treatment selection in the context of precision medicine. iBiopsy currently focuses on lung cancer, liver cancer (HCC) and liver fibrosis (NASH).

On March 3, 2022 CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) ("CNS" or the "Company"), a biopharmaceutical company specializing in the development of novel treatments for primary and metastatic cancers in the brain and central nervous system, reported its financial results for the year ended December 31, 2021 and provided a clinical update of its anti-cancer drug candidates currently in development for the treatment of primary and metastatic brain and CNS cancer (Press release, CNS Pharmaceuticals, MAR 3, 2022, View Source [SID1234609445]).

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2021 Key Highlights

May 2021: Commenced patient enrollment in the potentially pivotal study (CNS-201) evaluating efficacy of Berubicin in the treatment of adult recurrent Glioblastoma Multiforme (rGBM), one of the most aggressive types of brain cancer;
June 2021: FDA granted Fast Track Designation to CNS Pharmaceuticals for Berubicin for the treatment of recurrent GBM;
September 2021: Dosed first group of patients with Berubicin in the potentially pivotal study for the treatment of GBM;
December 2021: Received approval from "swissethics," the umbrella organization of the cantonal Ethics Committees (EC) in Switzerland, for the Company’s potentially pivotal study of Berubicin for the treatment of recurrent GBM; and
January 6, 2022: Announced a $11.5M private placement, priced at-the-market under Nasdaq rules.
"Operationally 2021 was a terrific year for the Company as we established the global framework for building and expanding our potentially pivotal clinical study of berubicin for the treatment of GBM. Our priority remains focused on advancing berubicin to bring a meaningful treatment to patients, families and clinicians, who currently have extremely limited and often ineffective treatment options. I am continually impressed by the speed and efficiency with which our small team has executed our Berubicin trial. At the onset of 2022 we completed a $11.5 million private placement which enables us to continue driving the development of berubicin this year towards the milestones ahead of us," commented John Climaco, CEO of CNS Pharmaceuticals. "While staying steadfast in our primary goal of bringing berubicin to GBM patients, we are also continually evaluating platform opportunities for expansion into additional oncology indications to bolster our pursuit of therapies for patients through developing novel treatments for primary and metastatic cancers. I am very pleased with the progress we’ve made over the past year, but am even more so looking forward to what lays ahead for CNS Pharmaceuticals."

Clinical Programs Update

Berubicin – Novel anthracycline

CNS’ lead product candidate, Berubicin, is a novel anthracycline and the first anthracycline to appear to cross the blood-brain barrier. Berubicin is currently in development for the treatment of a number of serious brain and CNS oncology indications. In mid-2021 the Company announced it has dosed the first group of patients in its potentially pivotal study evaluating the efficacy of Berubicin in the treatment of adult GBM, one of the most aggressive types of brain cancer. Further patient enrollment, randomization and dosing is currently underway as well as a robust lineup of clinical sites located globally which are advancing toward activation and enrollment.

The FDA granted CNS Pharmaceuticals Fast Track Designation for Berubicin which enables more frequent interactions with the FDA to expedite the development and review process. As previously announced, the Company also received Orphan Drug Designation from the FDA which may provide seven years of marketing exclusivity upon approval of an NDA.

For more information about the potentially pivotal Berubicin trial, visit clinicaltrials.gov and reference identifier NCT04762069.

Upcoming Milestones

Expand potentially pivotal study to evaluate efficacy of Berubicin in the treatment of adult GBM into additional countries;
Interim analysis of the trial when 30-50% of the total expected patients have been on study for 6 months (expected during first half of 2023); and
Complete enrollment in potentially pivotal clinical trial for GBM.
WP1244 Portfolio – Novel class of DNA-binding agents

The Company continues to advance the development of its WP1244 drug technology, which utilizes anthracycline and distamycin-based scaffolds to create small molecule agents and is believed to be 500x more potent than daunorubicin in inhibiting tumor cell proliferation. Preclinical studies of WP1244 demonstrated high uptake in the brain with antitumor activity. The Company’s development work has produced a new mesylate salt of WP1244, now identified as WP1874. The enhanced solubility of this salt may increase its ability to be formulated for use in an IV infusion, while maintaining similar potency and toxicity characteristics. Going forward, WP1874 will be the primary focus in our development efforts of the WP1244 portfolio. CNS Pharmaceuticals is also evaluating the use of WP1244/WP1874 in the treatment of other primary brain and central nervous system cancers, as well as cancers metastatic to the brain including pancreatic, ovarian, and lymphomas.

Upcoming Milestones

File IND in 2023.
Summary of Financial Results for the Full Year 2021

The net loss for the year ended December 31, 2021 was approximately $14.0 million compared to approximately $9.5 million for the comparable period in 2020. The change in net loss is attributable to increased personnel and activity associated with preparing for and commencing the Company’s potentially pivotal clinical trial of Berubicin for recurrent glioblastoma multiforme in 2021. The Company reported research and development expenses of $9.3 million for the year ended December 31, 2021 compared to approximately $5.1 million for the comparable period in 2020. The expenses incurred during the period were related to drug manufacturing and labor related to the preparation for and commencement of the Company’s potentially pivotal Berubicin study. General and administrative expense was approximately $4.7 million for the year ended December 31, 2021 compared to approximately $4.4 million for the comparable period in 2020.

As of December 31, 2021, the Company had cash of approximately $5.0 million and working capital of approximately $5.3 million. In early January 2022, the Company completed an offering of common stock and warrants for gross proceeds of $11.5 million. Our current expectation is that our cash on hand and the proceeds from the offering during January is sufficient to fund our operations into the first quarter of 2023. The timing and costs of clinical trials are difficult to predict and trial plans may change in response to evolving circumstances and as such the foregoing estimates may prove to be inaccurate.

On March 3, 2022 Cellectis (Euronext Growth: ALCLS – Nasdaq: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop potentially life-saving cell and gene therapies, reported its results for the fourth quarter of 2021, and full year ending December 31, 2021 (Press release, Cellectis, MAR 3, 2022, View Source [SID1234609461]).

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"In 2021, Cellectis presented encouraging preliminary data from patients who received fludarabine, cyclophosphamide and alemtuzumab preconditioning in the BALLI-01 study at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2021 annual meeting. BALLI-01 supports our mission to develop products for patients who remain in dire need of effective treatment options. These results showed that our preconditioning regimen, that included alemtuzumab, was well tolerated and promoted the expansion and clinical activity of UCART22 in patients with advanced B-cell Acute Lymphoblastic Leukemia. Both our Raleigh and Paris manufacturing facilities are now fully operational, with Paris producing plasmids, mRNA and viral vectors, and Raleigh manufacturing UCART22 and UCART20x22." said Dr. André Choulika, CEO of Cellectis.

"In 2022, we are focusing on patient recruitment into our three ongoing Phase 1 clinical trials BALLI-01, AMELI-01, MELANI-01, (evaluating UCART22, UCART123, and UCARTCS1 respectively) and plan to file an investigational new drug application (IND) in the U.S. for our first allogeneic dual CAR T-cell therapy, UCART20x22. To further support our clinical trials, and with both manufacturing sites now fully operational, we will start dosing patients with investigational medicinal products made in-house."

________________________
1 Cash position includes cash, cash equivalent, current financial assets and restricted cash. Restricted cash was $5million as of December 31, 2021.

Pipeline highlights

UCART Clinical Development Programs

BALLI-01 (evaluating UCART22) in relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL)

In December 2021, the Company reported preliminary results from the FCA arm of the BALLI-01 study of UCART22, for patients with r/r B-ALL at the 63rd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (ASH 2021).

Overall, UCART22 after FCA lymphodepletion regimen demonstrated promising signs of anti-leukemic activity at Dose Level 2 (DL2) and Dose Level 2 Intermediate (DL2i), without unexpected or significant treatment-related toxicity. The preliminary data shows that adding alemtuzumab to the fludarabine and cyclophosphamide (FC) lymphodepletion regimen did not adversely affect the overall safety profile and sustained host lymphocyte suppression and promoted expansion of UCART22.

BALLI-01 is currently enrolling patients at Dose Level 3 (DL3) with FCA preconditioning regimen and Cellectis plans to initiate dosing with a UCART22 product candidate manufactured in-house in H2 2022.
AMELI-01 (evaluating UCART123) in relapsed or refractory acute myeloid leukemia (r/r AML)

UCART123 is an allogeneic CAR T-cell product candidate targeting CD123 and being evaluated in patients with r/r AML in the AMELI-01, multi-center dose-escalation clinical study.

AMELI-01 is currently enrolling patients at DL2 with FCA preconditioning regimen.
MELANI-01 (evaluating UCARTCS1) in relapsed or refractory multiple myeloma (r/r MM)

UCARTCS1 is an allogeneic CAR T-cell product candidate targeting CS1 and is being evaluated in patients with r/r MM in the MELANI-01, multi-center dose-escalation clinical study.

In May 2021, early preliminary data from the first patients enrolled in the MELANI-01 trial were presented at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 24th annual meeting. The data validated CS1 as a target for allogeneic CAR T-cells in r/r MM. Moreover, UCARTCS1 expansion and persistence was observed and correlated with changes in relevant serum cytokines and with anti-myeloma activity.

Cellectis is currently enrolling patients at Dose Level 1 (DL1) with FC preconditioning regimen.
UCART Preclinical Programs

UCART20x22 in relapsed or refractory non hodgkin’s lymphoma (r/r NHL)

UCART20x22 is our first allogeneic dual CAR T-cell product candidate being developed for patients with r/r NHL. The dual targeting of CD20 and CD22, both validated targets in B-cell malignancies, is designed both for better tumor cell killing and to prevent antigen escape. Further, UCART20x22 is designed to be active against malignant B-cells that express one or both of the target antigens and to offer an alternative to CD19-directed therapies.

UCART20x22 will also be Cellectis’ first product candidate fully designed, developed and manufactured in-house, showcasing the Company’s transformation into an end-to-end cell and gene therapy platform from discovery, product development, GMP manufacturing, to clinical development.

An Investigational New Drug application (IND) for UCART20x22 is expected to be filed in 2022.
Licensed Allogeneic CAR-T Cell Development Programs

Allogene Therapeutics, Inc.’s CAR T programs utilize Cellectis technologies. ALLO-501 and ALLO-501A are anti-CD19 products being jointly developed under a collaboration agreement between Servier and Allogene based on an exclusive license granted by Cellectis to Servier. Servier grants to Allogene exclusive rights to ALLO-501 and ALLO-501A in the U.S. while Servier retains exclusive rights for all other countries. Allogene’s anti-BCMA and anti-CD70 programs are licensed exclusively from Cellectis by Allogene and Allogene holds global development and commercial rights to these programs.

On January 10, 2022, Allogene announced that the U.S. Food and Drug Administration (FDA) had removed the clinical hold on all of Allogene’s clinical trials which had been announced on October 7, 2021. After extensive investigation by Allogene, it was determined that the chromosomal abnormality detected in a single patient treated with ALLO-501A was unrelated to TALEN gene editing or Allogene’s manufacturing process and had no clinical significance.

Servier and Allogene: anti-CD19 programs

Allogene presented Phase 1 data from the ALPHA trial with ALLO-501 and ALPHA2 trial with ALLO-501A for the treatment of r/r NHL at the 2021 ASH (Free ASH Whitepaper) Annual Meeting. According to Allogene, data from these trials continue to support the promise of its platform to provide a safe and durable alternative to approved autologous CAR T therapies in CAR T naïve patients.

Enrollment in the Phase 1 ALLO-501 ALPHA trial in r/r NHL has completed accrual. Allogene disclosed that its focus remains on preparing for the pivotal Phase 2 ALPHA2 trial of ALLO-501A in R/R Large B Cell Lymphoma (LBCL), which Allogene reports to be on track to begin mid-year 2022 subject to ongoing discussions with the FDA.

As part of a concurrent development plan, Allogene intends to launch a separate registrational trial for ALLO-647, Allogene’s anti-CD52 monoclonal antibody, at the time of the ALLO-501A pivotal Phase 2 trial. This trial is intended to demonstrate the safety of ALLO-647 along with its contribution to the overall benefit of the lymphodepletion regimen.
Allogene: anti-BCMA and anti-CD70 programs

Following the FDA’s clinical hold, Allogene had announced that it has resumed clinical study activities on ALLO-715 and ALLO-605 for r/r MM, and ALLO-316 for advanced or metastatic clear cell renal cell carcinoma (RCC), and began enrolling patients earlier in February 2022.

Allogene’s anti-BCMA strategy includes its Phase 1 UNIVERSAL trial, which has cohorts evaluating ALLO-715 as a monotherapy, consolidated dosing of ALLO-715 using ALLO-647 to selectively extend the window of lymphodepletion, and ALLO-715 in combination with SpringWorks Therapeutics’ investigational gamma secretase inhibitor, nirogacestat.

Data from Allogene’s UNIVERSAL trial with ALLO-715 as a monotherapy for the treatment of r/r MM was also presented at ASH (Free ASH Whitepaper) 2021, with Allogene reporting that response rates that are similar to the approved autologous CAR T therapy.
Manufacturing Facilities

Cellectis’ starting materials manufacturing facility in Paris, France is now fully operational, focusing on the production of starting materials including plasmids and mRNA for our TALEN gene editing technology, and viral vectors for use in clinical manufacturing.

Cellectis’ UCART GMP manufacturing facility in Raleigh, North Carolina is now fully operational, focusing on Cellectis’ clinical and commercial UCART manufacturing operations as well as manufacturing and release testing of batches of product candidates UCART22 and UCART20x22.
Partnerships

Cytovia Therapeutics

On February 12, 2021, we entered into a research collaboration and non-exclusive license agreement with Cytovia Therapeutics, Inc., or Cytovia to develop induced Pluripotent Stem Cell (iPSC) iPSCderived Natural Killer (NK) and CAR-NK cells edited with our TALEN (the "Cytovia Agreement").
Pursuant to the Cytovia Agreement, as expanded in November 2021 to include a new CAR target and development in China by Cytovia’s joint venture entity, CytoLynx Therapeutics, Cellectis is eligible to receive an upfront cash payment or equity stake in Cytovia of $20 million, if certain conditions (the "Cytovia Conditions") were met by December 31, 2021, as well as aggregate additional payments of up to $805 million of development, regulatory and sales milestones from Cytovia. Cellectis is also eligible to receive single-digit royalty payments on the net sales of the partnered products commercialized by Cytovia. Cellectis also received an option to participate in certain future financing rounds by Cytovia. Cellectis is currently in discussions with Cytovia to grant a waiver and to extend the deadline for the Cytovia Conditions, which had not yet been achieved as of December 31, 2021.
Following Cellectis’ previously announced partnership with Iovance Biotherapeutics in tumor-infiltrating lymphocytes, the collaboration with Cytovia in another cell therapy modality highlights TALEN as a gene editing technology of choice for cell therapy applications.
2021 Corporate Highlights

Cellectis’ Innovation Days

In May 2021, Cellectis held a week-long virtual event, providing an inside look into the Company’s current and new product candidates pipeline, manufacturing and technologies. To watch a replay of all Cellectis Innovation Days episodes, click here.

Appointments

On November 4, 2021, Cellectis announced the appointment of Donald A Bergstrom, M.D., Ph.D., as an Observer on the Company’s Board of Directors. Dr. Bergstrom, serves as Executive Vice President, Head of Research and Development at Relay Therapeutics, Inc., a clinical-stage precision medicines company. He brings with him over 15 years of experience in the biopharmaceutical and medical industries.
On February 10, 2022, Cellectis announced the appointment of Bing Wang, Ph.D, MBA as Chief Financial Officer and member of Cellectis’ executive committee. Dr. Wang is a highly accomplished biotechnology executive who brings extensive global finance experience in the biotechnology industry including a background with global public companies in corporate finance, mergers and acquisitions, operations management systems, and financial planning and analysis. He joins Cellectis to oversee the company’s global finance team reporting directly to Chief Executive Officer, André Choulika, PhD.
ATM program

On March 29, 2021, Cellectis 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 $125.0 million of American Depositary Shares ("ADS"). Each ADS represents one ordinary share of the Company.
On April 9, 2021, the Company announced that it completed sales of approximately $47 million of ADS pursuant to the ATM program, comprising an aggregate of 2,415,630 new ADSs and the same number of underlying new ordinary shares were issued to existing and new investors at an at-the-market price of $19.50 per new ADS.
2021 Financial Results

The condensed consolidated financial statements of Cellectis, which consolidate the results of Calyxt, Inc. of which Cellectis is a 61.8% stockholder (as of December 31, 2021) and 56.1% as of March 3, 2022, have been prepared in accordance with International Financial Reporting Standards, as issued by the International Accounting Standards Board ("IFRS").

We present certain financial metrics broken out between our two reportable segments – Therapeutics and Plants – in the appendices of this Q4 2021 and Full Year 2021 financial results press release.

Fourth Quarter and Full Year 2021 Financial Results

Cash: As of December 31, 2021, Cellectis, including Calyxt, had $191 million in consolidated cash, cash equivalents, current financial assets and restricted cash of which $177 million are attributable to Cellectis on a stand-alone basis. This compares to $274 million in consolidated cash, cash equivalents, current financial assets and restricted cash as of December 31, 2020, of which $244 million was attributable to Cellectis on a stand-alone basis. This net decrease of $83 million primarily reflects (i) $116 million of net cash flows used in operating, investing and lease financing activities of Cellectis, (ii) $20 million of net cash flows used in operating, capital expenditures and lease financing activities of Calyxt and (iii) $6 million of unfavorable FOREX impact which was partially offset by (iv) $49 million of equity proceeds raised from sales under the Company’s "At-The-Market" (ATM) program in April 2021 and Calyxt ATM program during the fourth quarter of 2021 and (v) $10 million of proceeds from stock options exercises at Cellectis. Based on the current operating plan and financial projections, Cellectis excluding Calyxt anticipates that the cash, cash equivalents, and restricted cash of $177 million as of December 31, 2021 will fund its operations into early 2024.

Revenues and Other Income: Consolidated revenues and other income were $14 million for the three months ended December 31, 2021 compared to $16 million for the three months ended December 31, 2020. Consolidated revenues and other income were $67 million for the year ended December 31, 2021 compared to $82 million for the year ended December 31, 2020. 58% of consolidated revenues and other income was attributable to Cellectis in the full year of 2021. This decrease between the year ended December 31, 2021 and 2020 was mainly attributable to a $29 million upfront payment received in March 2020 and the recognition of $20 million of other previously-received upfront and milestone payments on the five released targets based on the March 2020 amendment of the License, Development and Commercialization Agreement signed with Servier. That was partially offset by (i) the recognition of a $20.0 trade receivable obtained as consideration for a license granted to Cytovia, (ii) $10.0 million related to the recognition of two Allogene milestones, (iii) the increase in sales of soybean products at Calyxt for $4 million, and (iv) Calyxt’s Paycheck Protection Program loan forgiveness obtained in April 2021 for 1.5 million, and is partially offset by a decrease in licenses revenues of $2 million.

Cost of Revenues: Consolidated cost of revenues were $2 million for the three months ended December 31, 2021 compared to $19 million for the three months ended December 31, 2020. Consolidated cost of revenues was $31 million for the year ended December 31, 2021 compared to $36 million for the year ended December 31, 2020. This decrease was primarily explained by the cost of products sold during the period by Calyxt.

R&D Expenses: Consolidated R&D expenses were $32 million for the three months ended December 31, 2021 compared to $23 million for the three months ended December 31, 2020. Consolidated R&D expenses were $129 million for the year ended December 31, 2021 compared to $87 million for the year ended December 31, 2020. 91% of consolidated R&D expenses was attributable to Cellectis in the full year of 2021. The $42 million increase between the full year of 2021 and 2020 was primarily attributable to (i) higher wages and salaries and social charges on stock option grants of $14 million, to (ii) higher purchases, external and other expenses of $25 million and to (iii) higher non-cash stock-based compensation expenses of $3 million.

SG&A Expenses: Consolidated SG&A expenses were $10 million for the three months ended December 31, 2021 compared to $12 million for the three months ended December 31, 2020. Consolidated SG&A expenses were $38 million for the year ended December 31, 2021 compared to $44 million for the year ended December 31, 2020. 60% of consolidated SG&A expenses was attributable to Cellectis in the full year of 2021. The $6 million decrease was mainly attributable to lower non-cash stock-based compensation expenses of $6 million and a decrease in wages and salaries of $1 million partially offset by an increase in social charges on stock option grants and purchases, external expenses and other of $1 million.

Net Income (loss) Attributable to Shareholders of Cellectis: The consolidated net loss attributable to shareholders of Cellectis was $25 million (or $0.55 per share) for the three months ended December 31, 2021, of which $21 million was attributed to Cellectis, compared to $41 million (or $0.95 per share) for the three months ended December 31, 2020, of which $34 million was attributed to Cellectis. The consolidated net loss attributable to shareholders of Cellectis was $114 million (or $2.55 per share) for the year ended December 31, 2021, of which $97 million loss was attributed to Cellectis, compared to a loss of $81 million (or $1.91 per share) for the year ended December 31, 2020, of which $54 million was attributable to Cellectis. This $33 million increase in net loss between full year 2021 and 2020 was primarily driven by a decrease in revenues and other income of $15 million and by an increase in operating expenses of $30 million and a decrease in non controlling interests of $5 million partially offset a by $18 million increase in net financial gain.

Adjusted Net Income (Loss) Attributable to Shareholders of Cellectis: The consolidated adjusted net loss attributable to shareholders of Cellectis was $22 million (or $0.48 per share) for the three months ended December 31, 2021, of which $19 million is attributed to Cellectis, compared to a net loss of $37 million (or $0.88 per share) for the three months ended December 31, 2020, of which $31 million was attributed to Cellectis. The consolidated adjusted net loss attributable to Shareholders of Cellectis was $102 million (or $2.27 per share) for the year ended December 31, 2021, of which $85 million loss was attributable to Cellectis, compared to a loss of $67 million (or $1.57 loss per share) for the year ended December 31, 2020, of which $44 million was attributable to Cellectis.

Please see "Note Regarding Use of Non-GAAP Financial Measures" for reconciliation of GAAP net income (loss) attributable to shareholders of Cellectis to adjusted net income (loss) attributable to shareholders of Cellectis.

We currently foresee focusing our cash spending at Cellectis for 2022 in the following areas:

Supporting the development of our pipeline of product candidates, including the manufacturing and clinical trial expenses of UCART123, UCART22, UCARTCS1, UCART20x22, and
Operating our manufacturing capabilities in Paris (France), and Raleigh (North Carolina, U.S.A);
and continuing to strengthen our manufacturing and clinical departments, including hiring talented, highly-qualified individuals
(1) When we have adjusted net loss, in accordance with IFRS, we use the Weighted average number of outstanding shares, basic to compute the Diluted adjusted net income (loss) attributable to shareholders of Cellectis ($/share). When we have adjusted net income, in accordance with IFRS, we use the weighted average number of outstanding shares, diluted to compute the diluted adjusted net income (loss) attributable to shareholders of Cellectis ($/share).

Conference Call and Webcast Details
Cellectis will host a live conference call and live audio webcast on March 4th, 2022 at 8AM EDT / 2:00PM CET to discuss fourth quarter and full year 2021 results and provide a business update.Webcast
Webcast link: View Source;tp_key=c23a20c39e

The webcast audio will be made available for one year on Cellectis’ website, linked here.

On March 3, 2022 "HUTCHMED" or the "Company (Nasdaq/AIM:​HCM; HKEX:​13) reported the retirement of Mr. Christian Hogg after almost 22 years with the Company, including 15 years as Executive Director and Chief Executive Officer ("CEO"); and the appointment of Dr. Weiguo Su, who has been with the Company for about 17 years, including about 10 years as Chief Scientific Officer ("CSO") and almost five years as Executive Director, as the new CEO (Press release, Hutchison China MediTech, MAR 3, 2022, View Source [SID1234609477]).

Dr. Su has been selected and appointed to his additional role as the CEO, as part of the Company’s ongoing succession planning. Since joining the Company in 2005, Dr. Su has been responsible for the establishment of all aspects of the oncology/immunology innovation platform which led to the in-house discovery of 12 novel oncology drug candidates of the Company, the first three of which have achieved approval and successful commercial launch. When assuming the new position, Dr. Su will combine the crucial research and development function of the Company for which he has been responsible, with the lead executive role as the CEO.

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Prior to HUTCHMED, Dr. Su, aged 64, spent fifteen years in the U.S. Research and Development organization of Pfizer, Inc. and before that, seven years completing his PhD and Post-Doctoral Fellowship in Chemistry at Harvard University under the guidance of Nobel Laureate, Professor E. J. Corey. Dr. Su received a Bachelor of Science degree in Chemistry from Fudan University in Shanghai.

In March 2017, Dr. Su was granted the prestigious award by the China Pharmaceutical Innovation and Research Development Association (PhIRDA) as one of the Most Influential Drug R&D Leaders in China.

While Dr. Su will remain as the CSO for the time being, as part of the ongoing succession planning of the Company, Dr Su, the Nomination Committee and the Board will identify appropriate candidates to take up the leadership of its research and development function.

Mr. Christian Hogg, retiring CEO of HUTCHMED, said "After over 34 years away, and 27 years in China, I have taken the decision to return home to Europe to focus on, and be close to, my important family responsibilities. I am glad to see the Board’s new appointment of Dr. Weiguo Su, one of the industry’s most respected leaders, and a person who I believe, with the support of our board and deeply experienced senior management team, will take HUTCHMED to greater heights. I would like to thank all HUTCHMED colleagues and stakeholders for the support they have given me and I look forward to their continued success."

Mr. Simon To, Chairman of HUTCHMED said, "Christian was the first employee of HUTCHMED twenty-two years ago and he has worked tirelessly to build the Company from its very beginning into the truly globally facing biopharmaceutical company it is today. Christian will remain as a strategic advisor to the Company, with an emphasis on organizational development, relations with our partners, global commercialization strategy and investor relations matters."

Mr. To continued, "On behalf of the Board, I would like to congratulate Dr. Su on his appointment to CEO of HUTCHMED, and wish him great success in this well-deserved appointment. I would also like to extend our deepest appreciation to Christian for his contributions and wish him the best in his retirement."

The change to the position of CEO will take effect on March 4, 2022. Also effective from the same date, Mr. Hogg will cease to be a member of the Sustainability Committee and the Technical Committee of the Company.

Mr. Hogg has confirmed that he has no disagreement with the Board, and that there are no other matters that need to be brought to the attention of the shareholders of the Company in connection with his retirement.

Further information about Dr. Su and his appointment
Dr. Su does not have any relationship with any other Directors, senior management, substantial or controlling shareholders of the Company. As at the date of this announcement, Dr. Su had a personal interest in 6,833,580 ordinary shares in the Company ("Shares"), representing approximately 0.79% of the number of Shares in issue, within the meaning of Part XV of the Securities and Futures Ordinance. The term of Dr. Su’s service as an Executive Director of the Company is subject to retirement by rotation and re-election at the annual general meeting of the Company. The director’s fees of Dr. Su as an Executive Director and a member of the Technical Committee of the Company under his appointment letter are US$70,000 and US$5,000 per annum respectively. The emoluments specified in the service agreement appointing Dr. Su as CEO and CSO of the Company are US$1,959,300 per annum in salary and cash bonus. There will also be equity compensation of up to US$4,440,700 per annum, including performance based and non-performance based portions. Such emoluments are determined by reference to the performance and profitability of the Company as well as his personal performance, remuneration benchmark in the industry and the prevailing market conditions. Such amounts are subject to review from time to time and proration for an incomplete year of service.

There are no other matters concerning Dr. Su that are required to be brought to the attention of the shareholders, nor is there other information that is required to be disclosed pursuant to the requirements of Rule 13.51(2) of the Rules Governing the Listing of Securities on the Stock Exchange of Hong Kong Limited and Rule 17 of the AIM Rules for Companies.