On June 21, 2022 Celsion Corporation (NASDAQ: CLSN), a clinical-stage company focused on DNA-based immunotherapy and next-generation vaccines, reported that following a pre-planned interim safety review of 87 as treated patients (46 patients in the experimental arm and 41 patients in the control arm) randomized in the Phase I/II OVATION 2 Study with GEN-1 in advanced (Stage III/IV) ovarian cancer, the Data Safety Monitoring Board (DSMB) has unanimously recommended that the OVATION 2 Study continue treating patients with the dose of 100 mg/m2 (Press release, Celsion, JUN 21, 2022, View Source [SID1234616112]). The DSMB also determined that safety is satisfactory with an acceptable risk/benefit, and that weekly doses of GEN-1 were well tolerated during a course of treatment that is given over six months in combination with standard neoadjuvant chemotherapy. No dose-limiting toxicities were reported.

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The OVATION 2 Study combines GEN-1, the Company’s IL-12 gene-mediated immunotherapy, with standard-of-care neoadjuvant chemotherapy (NACT) in patients newly diagnosed with Stage III/IV ovarian cancer. NACT is designed to shrink the cancer as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT, patients undergo interval debulking surgery, followed by three additional cycles of chemotherapy to treat any residual tumor.

The OVATION 2 Study is designed with an 80% confidence interval to show an approximate 33% improvement in risk for cancer progression, Progression Free Survival, when comparing the treatment arm (NACT + GEN-1) with the control arm (NACT only). GEN-1 is an immunotherapy that produces safe and durable local levels of IL-12, a pluripotent cytokine associated with the stimulation of innate and adaptive immune response against cancer. The GEN-1 nanoparticle comprises a DNA plasmid encoding IL-12 gene and a synthetic polymer facilitating plasmid delivery vector. Cell transfection is followed by persistent, local secretion of the IL-12 protein at therapeutic levels.

The Company also announced that more than 87% of the projected 110 patients have been enrolled in the OVATION 2 Study. Interim clinical data from patients who have undergone interval debulking surgery showed that the GEN-1 treatment arm is showing improvement in R0 surgical resection rates and CRS 3 chemotherapy response scores over the control arm. A complete tumor resection (R0) is a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed. The chemotherapy response score is a three-tier standardized scoring system for histological tumor regression into complete/near complete (CRS 3), partial (CRS 2) and no/minimal (CRS 1) response based on omental examination.

"Findings from our OVATION 2 study show a consistent favorable trend in both surgical outcome and tumor response, which is further supported by translational data of the tumor microenvironment," noted Nicholas Borys, M.D., Celsion’s executive vice president and chief medical officer. "We are encouraged by the current rate of patient recruitment and expect to complete enrollment by the third quarter of 2022. The primary endpoint for the study is progression-free survival (PFS) which we expect to report approximately 12 months after patient enrollment is completed."

In February 2021, the Company announced that GEN-1 received FDA Fast Track Designation in advanced ovarian cancer. Celsion plans to request FDA Breakthrough Therapy Designation for GEN-1 based on the encouraging clinical data.

"We again want to thank the DSMB members for their work and advice," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "Preclinical and clinical data gives us every reason to believe in GEN-1’s promise for ovarian cancer patients along with the support from leading medical researchers of the Gynecological Oncology Group (GOG). FDA Fast Track Designation for GEN-1 in advanced ovarian cancer coupled with the GOG’s interest in forging a partnership to develop GEN-1 in ovarian cancer will assist Celsion in its plans for an accelerated registrational program."

About GEN-1 Immunotherapy

GEN-1, designed using Celsion’s proprietary TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation. The Company previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy or a combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer, and recently completed a Phase Ib dose-escalation trial (OVATION 1 Study) of GEN-1 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer.

About Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is the fifth deadliest malignancy among women in the United States. There are approximately 22,000 new cases of ovarian cancer every year and the majority (approximately 70%) are diagnosed in advanced stages III and IV. EOC is characterized by dissemination of tumor in the peritoneal cavity with a high risk of recurrence (75%, stage III and IV) after surgery and chemotherapy. Since the five-year survival rates of patients with stages III and IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for regional approach to immune modulation.

On June 21, 2022 Phanes Therapeutics, Inc. (Phanes), an emerging leader in innovative discovery research and clinical development in oncology, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to PT217 for the treatment of small cell lung cancer (SCLC) (Press release, Phanes Therapeutics, JUN 21, 2022, View Source [SID1234616146]).

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PT217 is a first-in-class bispecific antibody targeting Delta-like ligand 3 (DLL3) and cluster of differentiation 47 (CD47) being developed for patients with SCLC and other neuroendocrine cancers. SCLC is an aggressive pulmonary carcinoma hallmarked by high early mortality rates and significant morbidities throughout the disease’s progression. The 1-year survival of patients with SCLC is only 32.9%, with only 10.7% of patients surviving 3 years.

"PT217 has the potential to be a transformative treatment option for SCLC patients whose initial response to chemotherapy is short-lived and inevitably becomes resistant to chemotherapeutic agents" said Dr. Ming Wang, Founder and CEO of Phanes Therapeutics. "We have built a strong pipeline in immuno-oncology by leveraging our proprietary technology platforms and expect to file an IND for PT217 by the third quarter of this year. This orphan drug designation follows two recent IND clearances for our PT199, an anti-CD73 monoclonal antibody and PT886, an anti-Claudin 18.2/anti-CD47 bispecific antibody, programs which we are progressing into the clinic."

The FDA’s Office of Orphan Products Development grants orphan designation status to drugs and biologics that are intended to treat, diagnose, or prevent rare diseases that affect fewer than 200,000 people in the United States. Orphan drug designation provides certain benefits, including financial incentives to support clinical development and the potential for up to seven years of market exclusivity in the U.S. upon regulatory approval.

On June 21, 2022 Evotec reported that A consortium of strong partners has launched the CARMA FUND I as a new vehicle for the translation of promising early-stage life-science projects: the initiators, Ascenion GmbH, a life-science focused technology transfer company of the LifeScience Foundation and the Goethe-University, Frankfurt am Main with its technology transfer company Innovectis GmbH, together with the European Investment Fund (EIF) and other investors (Press release, Evotec, JUN 21, 2022, View Source [SID1234616113]). The fund will be managed by CARMA FUND Management GmbH, headed by its general partners Christian Leikert and Martin Raditsch.

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The fund, with a target size of € 60 m and a first closing at € 47 m, will invest in promising start-ups or high-potential academic projects in the life-science field, from Ascenion’s and Innovectis’ partner institutions. However, outstanding innovations or spin-offs from other German or European research organizations will also be considered as investment targets. Projects will be selected for their scientific excellence and potential to deliver outstanding societal or patient benefits and financial returns. CARMA is open to the full breadth of life-science and medical innovation, including new therapeutic and diagnostic approaches, platform technologies, medical devices and digital health. Along with funding, the projects will benefit from the partners’ network of distinguished top-level industry representatives and experts.

For further information, please follow this link to the press releases from Goethe-University, Frankfurt am Main and Ascenion, respectively.

On June 21, 2022 Arcellx, Inc. (NASDAQ: ACLX), a biotechnology company reimagining cell therapy through the development of innovative immunotherapies for patients with cancer and other incurable diseases, reported the closing of its upsized public offering of 8,050,000 shares of common stock, which includes the full exercise by the underwriters of their option to purchase an additional 1,050,000 shares of common stock, at a price to the public of $16.00 per share (Press release, Arcellx, JUN 21, 2022, View Source [SID1234616131]). The aggregate gross proceeds raised in the offering were $128.8 million, before deducting underwriting discounts and commissions and offering expenses, payable by Arcellx. All shares in the offering were offered by Arcellx.

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BofA Securities, SVB Securities, William Blair and Canaccord Genuity acted as joint book-running managers for the offering.

Registration statements relating to the offering have been filed with the Securities and Exchange Commission and became effective on June 15, 2022. The offering was made only by means of a prospectus, forming a part of the registration statements, copies of which may be obtained from: BofA Securities, NC1-004-03-43, 200 North College Street, 3rd Floor, Charlotte, NC 28255-0001, Attention: Prospectus Department, or by email at [email protected]; or SVB Securities LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, Massachusetts 02109, by telephone at 1-800-808-7525, ext. 6105, or by email at [email protected]. William Blair & Company, L.L.C., Attention: Prospectus Department, 150 North Riverside Plaza, Chicago, IL 60606, by telephone at 1-800-621-0687, or by email at [email protected]; or Canaccord Genuity LLC, Attention: Syndicate Department, 99 High Street, 12th Floor, Boston, MA 02110, or by telephone at (617) 371-3900, or by email at [email protected]. Copies of the registration statements and the final prospectus related to the offering are also available at www.sec.gov.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

On June 21, 2022 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported progress on its parallel lead clinical programs NVL-520, a novel ROS1-selective inhibitor, and NVL-655, a novel ALK-selective inhibitor (Press release, Nuvalent, JUN 21, 2022, View Source [SID1234616147]). Nuvalent announced that it plans to share preliminary data from the dose-escalation portion of its ongoing ARROS-1 Phase 1/2 clinical trial for NVL-520 in patients with advanced ROS1-positive NSCLC and other solid tumors in the second half of 2022. In addition, Nuvalent announced that the first patient has been dosed in ALKOVE-1, its Phase 1/2 clinical trial evaluating NVL-655 in patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors. NVL-520 and NVL-655 have been designed to address the clinical challenges of emergent treatment resistance, off-target CNS adverse events, and brain metastases that may limit the use of currently available ROS1 and ALK kinase inhibitors.

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"Advancing two novel candidates into clinical development in a little over six months is a significant achievement that we believe demonstrates our ability to scale as a clinical stage company with our growing portfolio, and the value of continued collaboration with leading physician-scientists in the advancement of investigational opportunities for patients in need of new therapies," said Christopher Turner, M.D., Chief Medical Officer of Nuvalent. "We remain committed to the efficient and data-driven development of NVL-520 and NVL-655 through our ARROS-1 and ALKOVE-1 studies and look forward to the opportunity to share preliminary data from the dose-escalation portion of the ARROS-1 trial later this year."

ARROS-1 is a Phase 1/2, multicenter, open-label, dose-escalation and expansion trial evaluating NVL-520 in patients with advanced ROS1-positive NSCLC and other solid tumors. ARROS-1 is actively enrolling patients with previously treated ROS1-positive solid tumors in the Phase 1 portion of the study. Additional information on the ARROS-1 trial is available on www.ClinicalTrials.gov (NCT05118789).

ALKOVE-1 is a Phase 1/2, multicenter, open-label, dose-escalation and expansion trial evaluating NVL-655 in patients with advanced ALK-positive NSCLC and other solid tumors. The Phase 1 dose-escalation portion of the study is open and enrolling patients with previously treated ALK-positive solid tumors and will evaluate the overall safety and tolerability of NVL-655. Additional objectives include determination of the recommended Phase 2 dose (RP2D), characterization of the pharmacokinetic profile, and evaluation of preliminary anti-tumor activity.

Once a safe and tolerable dose is determined as the RP2D, the ALKOVE-1 trial is designed to transition directly into the Phase 2 multiple cohort expansion portion, which will evaluate the overall activity of NVL-655 in patients with advanced ALK-positive NSCLC and other solid tumors. The Phase 2 portion will examine several cohorts of patients based on the number and type of prior anti-cancer therapies they have received. The Phase 2 cohorts are designed with the intent to expand in size, as data emerge and in collaboration with the U.S. Food and Drug Administration (FDA), into potential registrational cohorts for the treatment of previously treated patients with ALK-positive NSCLC. Additional information on the ALKOVE-1 trial is available on www.ClinicalTrials.gov (NCT05384626).

"The ALKOVE-1 study has been designed with the goal of seamlessly accelerating from first-in-human dose-exploration of NVL-655 into Phase 2 cohorts evaluating a range of ALK-positive patient populations," said Darlene Noci, A.L.M., Senior Vice President of Product Development & Regulatory Affairs for Nuvalent. "We believe the growing body of preclinical data generated to date for NVL-655 continue to demonstrate its promise as a differentiated ALK-selective inhibitor with the potential to overcome the limitations of currently available therapies, and are supportive of its development throughout the treatment paradigm for patients with ALK-positive cancers."

In addition to NVL-520 and NVL-655, Nuvalent continues to advance its pipeline expansion efforts with multiple discovery-stage research programs.

About NVL-520
NVL-520 is a brain-penetrant ROS1-selective inhibitor designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with the prevalent G2032R resistance mutation and those with the S1986Y/F, L2026M, or D2033N resistance mutations. NVL-520 has been optimized for brain penetrance to potentially improve treatment options for patients with brain metastases. NVL-520 has been observed in preclinical studies to selectively inhibit wild-type ROS1 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/ROS1 inhibitors and drive more durable responses for patients. NVL-520 is currently being investigated in the ARROS-1 study (NCT05118789), a first-in-human Phase 1/2 clinical trial for patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors.

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.