Celularity Announces Treatment of First Patient in Phase 1/2a Clinical Trial for NK Cell Therapy CYNK-101, in Development for the First-Line Treatment of Advanced HER2 Positive Gastric and Gastroesophageal Junction (G/GEJ) Cancers

On July 27, 2022 Celularity Inc. (Nasdaq: CELU) ("Celularity"), a clinical-stage biotechnology company developing placental-derived off-the-shelf allogeneic cell therapies, reported that the first patient has been treated with CYNK-101, a novel allogeneic off-the-shelf human placental CD34+ stem cell derived NK cell therapeutic candidate that is genetically modified to express high-affinity and cleavage-resistant CD16 (FCGRIIIA) variant to enhance antibody-dependent cell-mediated cytotoxicity (ADCC) (Press release, Celularity, JUL 27, 2022, View Source;utm_medium=rss&utm_campaign=treatment-of-first-patient-in-phase-1-2a-clinical-trial-for-nk-cell-therapy-cynk-101-in-development-for-the-first-line-treatment-of-advanced-her2-positive-gastric-and-gastroesophageal-junction-cancers [SID1234616983]). Earlier this year, CYNK-101 was granted both a Fast Track Designation and an Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of human epidermal growth factor receptor 2 (HER2) positive G/GEJ cancer.

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"It is well understood that gastric cancer has less than desirable survival outcomes," said Robert Hariri, M.D., Ph.D., Founder, Chairman and Chief Executive Officer of Celularity. "CYNK-101 is built on the foundation of our unique placental-derived source material, which as compared to other cell sources has naturally enhanced proliferative potential, or stemness, that has been shown to be a determinant of persistence and efficacy potential. Using novel genetic engineering, we enhance the ability of CYNK-101 cells to synergize with approved antibodies and provide a novel, potentially non-cross resistant therapy that we believe will be effective in improving the lives of patients with G/GEJ cancers as well as a broad range of other indications."

Dr. Darren Sigal, head of the gastrointestinal cancer section at The Scripps Cancer Research Institute, commented, "The dosing of the first patient in Celularity CYNK-101 gastric cancer program is an exciting milestone in the clinical development of cell therapies in solid tumors. NK cells possess inherent direct anti-solid tumor activity, recruit non-cross resistant anti-tumor T cells, and may induce memory T cells for long-term anti-cancer immune surveillance."

Dr. Martin Gutierrez, principal investigator and Chief of Thoracic Oncology at John Theurer Cancer Center – Hackensack Meridian Health who treated the first patient said, "We believe NK cells are poised to be the key components of multipronged therapeutic strategies for cancer. It is our understanding that we administered what is the highest dose of allogeneic NK cells so far over a 21-day period. Those cells were derived from human placental hematopoietic stem/progenitor cells and genetically modified to express a variant of CD16 to enable high affinity and enhance antibody dependent cell mediated cytotoxicity. We administered 36 X 106 transduced CYNK-101/kg weekly for four weeks in combination with pembrolizumab and trastuzumab to a patient with Her2 positive gastroesophageal carcinoma. All infusions occurred in the outpatient setting."

Phase 1/2a Clinical Trial of CYNK-101 in Gastric Cancer

CYNK-101 is currently being investigated in the Phase 1 portion of a multicenter Phase 1/2a clinical trial to evaluate the safety and preliminary efficacy of CYNK-101 in combination with trastuzumab and pembrolizumab, as a first-line treatment in patients with locally advanced unresectable or metastatic HER2 positive gastric/gastroesophageal (G/GEJ) adenocarcinoma. This study is utilizing a 3+3 open label design and will evaluate two escalating dosing cohort levels of CYNK-101 in combination with rhIL2 following an initial induction and lymphodepletion regimen. Once the maximum tolerated dose or recommended Phase 2 dose is determined in Phase 1, the Phase 2a portion of the study will commence (NCT05207722).

About Gastric Cancer

Gastric cancer is the fifth most common cancer worldwide. Advanced gastric cancer remains one of the hardest to cure, with a median overall survival (OS) of 10–12 months and a five-year OS of about 5–20%. Approximately 22% of patients with advanced gastric cancer have human epidermal growth factor receptor 2 (HER2) overexpression or amplification.

About CYNK-101

Celularity’s therapeutic candidate based on its placental-derived genetically modified NK cell type is CYNK-101, an allogeneic, off-the-shelf human placental CD34+-derived NK cell product genetically modified to express high-affinity and cleavage-resistant CD16 (FCGRIIIA) variant to drive antibody-dependent cell-mediated cytotoxicity. Currently CYNK-101 is being developed as a treatment in combination with standard chemotherapy, trastuzumab and pembrolizumab for HER2 positive overexpressing gastric or gastroesophageal junction adenocarcinoma. The safety and efficacy of CYNK-101 have not been established, and CYNK-101 has not been approved for any use by the FDA or any other analogous regulatory authority.

Bristol Myers Squibb Reports Second Quarter Financial Results for 2022

On July 27, 2022 Bristol Myers Squibb (NYSE:BMY) reported that results for the second quarter of 2022, which reflect continued in-line product growth, strong momentum across the new product portfolio and continued pipeline progress (Press release, Bristol-Myers Squibb, JUL 27, 2022, View Source [SID1234616982]).

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"I am very pleased with the continued strong demand for our in-line products and new product portfolio, resulting in solid top and bottom-line growth," said Giovanni Caforio, M.D., board chair and chief executive officer, Bristol Myers Squibb. "The momentum with our business and strength of our pipeline, gives us significant opportunities to drive continued growth, starting with the anticipated approval for deucravacitinib in moderate to severe plaque psoriasis and the expected transition of milvexian, our next generation anti-thrombotic, to phase 3 development. With our financial strength and dedicated workforce, we are well positioned to help more patients and drive long-term value for our shareholders."

1 Acquired IPRD refers to certain in-process research and development ("Acquired IPRD") charges resulting from upfront or contingent milestone payments in connection with asset acquisitions or licensing of third-party intellectual property rights.

Second Quarter

$ amounts in millions, except per share amounts

* GAAP and non-GAAP earnings per share include the net impact of Acquired IPRD charges and licensing income of ($0.14) per share in the second quarter of 2022 and ($0.30) per share in the second quarter of 2021.

SECOND QUARTER FINANCIAL RESULTS

All comparisons are made versus the same period in 2021 unless otherwise stated.

Bristol Myers Squibb posted second quarter revenues of $11.9 billion, an increase of 2%, driven by in-line products (primarily Eliquis and Opdivo) and new product portfolio (Abecma, Opdualag and Reblozyl), partially offset by recent LOE products (primarily Revlimid)and foreign exchange impacts. When adjusted for foreign exchange impacts, second quarter revenues increased 5%.
U.S. revenues increased 12% to $8.3 billion in the quarter. International revenues decreased 16% to $3.6 billion in the quarter. When adjusted for foreign exchange impacts, international revenues decreased 8%, primarily due to lower demand of Revlimid as a result of generic erosion, partially offset by in-line products (primarily Opdivo and Eliquis) and our new product portfolio.
Gross margin decreased from 79.0% to 77.1% in the quarter primarily due to product mix and an impairment charge resulting from the divestiture of a manufacturing site, partially offset by foreign exchange impacts and related hedging settlements. On a non-GAAP basis, gross margin decreased from 79.8% to 78.3% in the quarter primarily driven by product mix, partially offset by foreign exchange impacts and related hedging settlements.
Marketing, selling and administrative expenses decreased 5% to $1.8 billion in the quarter on a GAAP and non-GAAP basis primarily due to foreign exchange impacts.
Research and development expenses decreased 6% to $2.3 billion in the quarter primarily due to an in-process research and development (IPRD) impairment charge in 2021, partially offset by increased investment in our broad and diversified portfolio. On a non-GAAP basis, research and development expenses increased 2% to $2.3 billion in the quarter primarily due to investment in our broad and diversified pipeline.
Acquired IPRD decreased from $793 million in the same period a year ago to $400 million in the current quarter. Acquired IPRD in the current quarter primarily related to the buyout of a future royalty obligation related to mavacamten ($295 million) and the BridgeBio licensing transaction ($90 million). Acquired IPRD in the same period a year ago was primarily related to a collaboration agreement with Eisai ($650 million).
Amortization of acquired intangible assets decreased 5% to $2.4 billion in the quarter primarily due to a longer than previously expected market exclusivity period for Pomalyst.
The GAAP effective tax rate changed from 31.7% to 27.0% in the quarter and non-GAAP effective tax rate changed from 17.6% to 17.0% in the quarter due to jurisdictional earnings mix including income taxes attributed to Acquired IPRD charges.
The company reported net earnings attributable to Bristol Myers Squibb of $1.4 billion, or $0.66 per share, in the second quarter, compared to $1.1 billion, or $0.47 per share, for the same period a year ago. In addition to the items discussed above, the results include the impact of fair value adjustments on equity investments in both periods.
The company reported non-GAAP net earnings attributable to Bristol Myers Squibb of $4.2 billion, or $1.93 per share, in the second quarter, compared to non-GAAP net earnings of $3.7 billion, or $1.63 per share, for the same period a year ago.
In addition to the items discussed above, the earnings per share results in the current period include the impact of lower weighted-average common shares outstanding.
Beginning with the first quarter of 2022, significant R&D charges or other income resulting from upfront or contingent milestone payments in connection with asset acquisitions or licensing of third-party intellectual property rights are no longer excluded from non-GAAP results. These R&D charges that were previously specified are now presented in a new financial statement line item labeled Acquired IPRD. GAAP and non-GAAP earnings per share include the net impact of Acquired IPRD charges and licensing income of ($0.14) per share in the second quarter of 2022 and ($0.30) per share in the second quarter of 2021. For purposes of comparability, the non-GAAP financial results for the second quarter of 2021 have been updated to reflect this change. A discussion of the non-GAAP financial measures is included under the "Use of Non-GAAP Financial Information" section.

SECOND QUARTER PRODUCT REVENUE HIGHLIGHTS

* In excess of +100%
** Includes over-the-counter (OTC) products, royalty revenue and other mature products.

FIRST HALF PRODUCT REVENUE HIGHLIGHTS

* In excess of +100%
** Includes over-the-counter (OTC) products, royalty revenue and other mature products.

REVENUE HIGHLIGHTS

In-Line Products

Revenues for in-line products in the second quarter were $8.7 billion compared to $8.0 billion in the prior year period, representing an increase of 9%. In-line products revenue was largely driven by:

Eliquis revenues grew 16% compared to the prior year period. U.S. revenues were $2.2 billion compared to $1.7 billion in the prior year period, representing an increase of 27% driven primarily by demand growth and favorable gross to net adjustments. International revenues were $1.0 billion compared to $1.1 billion in the prior year period, representing a decrease of 3% driven by foreign exchange impacts, partially offset by higher demand.
Opdivo revenues increased 8% compared to the prior year period. U.S. revenues were $1.2 billion compared to $1.1 billion in the prior year period, representing an increase of 12% driven by higher demand across multiple indications including Opdivo plus Yervoy-based combinations for non-small cell lung cancer, Opdivo plus Cabometyx combination for kidney cancer, and Opdivo-based therapies for various gastric, bladder and esophageal cancers, partially offset by declining second-line eligibility across tumors and increased competition. International revenues were $858 million compared to $834 million in the prior year period, representing an increase of 3% driven by higher demand as a result of launches for additional indications and core indications, partially offset by foreign exchange impacts of 10%.
New Product Portfolio

New product portfolio revenues grew to $482 million compared to $225 million in the prior year period, driven by higher demand for Abecma, Opdualag and Reblozyl.
Recent LOE Products

Revlimid revenues declined by 22% compared to the prior year period. U.S. revenues decreased 2% to $2.1 billion as compared to the prior year period primarily driven by lower demand as a result of generic erosion. International revenues were $371 million compared to $1.0 billion in the prior year period, representing a decrease of 64% driven by lower demand as a result of generic erosion and to a lesser extent, foreign exchange impacts of 3%.
Abraxane revenues declined 19% compared to the prior year period. U.S. revenues were $176 million compared to $234 million in the prior year period, representing a 25% decline driven by the entry of authorized generics.
PRODUCT AND PIPELINE UPDATE

Oncology

Category

Asset

Milestone

Regulatory

OpdualagTM

(nivolumab and relatlimab-rmbw)

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of Opdualag for the first-line treatment of advanced (unresectable or metastatic) melanoma in adults and adolescents 12 years of age and older with tumour cell PD-L1 expression <1%. The positive opinion is based on results from the Phase 2/3 RELATIVITY -047 trial.

Regulatory

Opdivo(nivolumab)

The U.S. Food and Drug Administration (FDA) approved Opdivo (injection for intravenous use) in combination with fluoropyrimidine- and platinum-containing chemotherapy as well as Opdivo plus Yervoy as first-line treatments for adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma regardless of PD-L1 status. The approvals are based on results from the Phase 3 CheckMate -648 trial.

Clinical & Research

Five-year follow up results from Part 1 of the Phase 3 CheckMate -227 trial demonstrated long-term, durable survival outcomes with Opdivo plus Yervoy compared to chemotherapy in first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC), regardless of PD-L1 expression levels. In the primary endpoint population, the combination nearly doubled overall survival rate compared to chemotherapy.

Three-year follow up results from the Phase 3 CheckMate -9LA trial demonstrated long-term, durable survival benefits with Opdivo plus Yervoy with two cycles of chemotherapy compared to four cycles of chemotherapy in patients with previously untreated metastatic NSCLC, regardless of PD-L1 expression and histology.

Phase 3 CheckMate -901 trial comparing Opdivo plus Yervoy to standard-of-care chemotherapy as a first-line treatment for patients with untreated unresectable or metastatic urothelial carcinoma who are ineligible for cisplatin-based chemotherapy, did not meet the primary endpoint of overall survival in patients whose tumor cells express PD-L1 ≥1% at final analysis.

Hematology

Category

Asset

Milestone

Regulatory

Breyanzi

(lisocabtagene maraleucel)

The FDA approved Breyanzi for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after one prior therapy, including diffuse LBCL not otherwise specified, high-grade B-cell lymphoma, primary mediastinal LBCL and follicular lymphoma grade 3B, who relapse within 12 months of first-line chemoimmunotherapy or who are not eligible for transplant. The approval was based on the pivotal Phase 3 TRANSFORM trial as well as the Phase 2 PILOT study.

The EMA validated the type II variation application for extension of the indication of Breyanzi for the treatment of adults with LBCL who are refractory or have relapsed within 12 months of initial therapy and are candidates for hematopoietic stem cell transplant. The EMA validation is based on results from the Phase 3 TRANSFORM trial.

Reblozyl

(luspatercept-aamt)

The company withdrew a supplemental biologics license application for Reblozyl for the treatment of anemia in adults with non-transfusion-dependent beta thalassemia.

Clinical & Research

Breyanzi

Data from the primary analysis of the Phase 2 PILOT trial showed substantial durable responses in second-line LBCL among patients who were not deemed candidates for high-dose chemotherapy and hematopoietic stem cell transplant.

Immunology

Category

Asset

Milestone

Clinical & Research

Orencia(abatacept)

Top-line results from the Phase 3 Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-1) Immune Modulators clinical trial, sponsored by the National Institutes of Health, showed that treatment with Orencia versus placebo displayed a strong, but not statistically significant improvement in the primary endpoint of time to recovery as measured by day of hospital discharge. Analyses of the secondary endpoints, which included mortality and clinical status, demonstrated Orencia reduced participants’ risk of death and improved their clinical status at 28 days after entering the study when compared with placebo.

deucravacitinib

Results from the Phase 2 PAISLEY trial showed statistically significant efficacy at the primary endpoint of Systemic Lupus Erythematosus (SLE) Responder Index-4 responses at Week 32 among patients with moderate to severe SLE who were treated with deucravacitinib versus placebo. Secondary endpoints demonstrated clinically meaningful improvements at Week 48. The safety profile was consistent with previous trials in psoriasis and psoriatic arthritis. Data demonstrated favorable risk-benefit profile supportive of progressing into Phase 3.

Two-year results from the Phase 3 POETYK PSO long-term extension (LTE) trial demonstrated durable efficacy and a consistent safety profile in adult patients with moderate to severe plaque psoriasis.

Zeposia

(ozanimod)

Post-hoc analyses from the Phase 3 DAYBREAK open-label extension and Phase 3 SUNBEAM trialsshowed that the majority of patients receiving Zeposia for multiple sclerosis reported improved or preserved cognitive function, with the greatest improvement seen when used early in the disease when thalamic volume remains high.

Results from an analysis from the ongoing Phase 3 DAYBREAK open-label extension trial showed that individuals receiving Zeposia for multiple sclerosis demonstrated an immune response to COVID-19 vaccination.

Business Development

In June, the company and Turning Point Therapeutics, Inc. ("Turning Point") (NASDAQ:TPTX) announced a definitive merger agreement under which Bristol Myers Squibb will acquire Turning Point pursuant to a tender offer for $76.00 per share, in an all cash transaction totaling approximately $4.1 billion. The planned acquisition is expected to expand the company’s precision oncology and solid tumor portfolio with the addition of repotrectinib and other pipeline assets. Repotrectinib is a potential best-in-class tyrosine kinase inhibitor targeting the ROS1 and NTRK oncogenic drivers of non-small cell lung cancer and other advanced solid tumors. The consummation of the transaction is subject to the satisfaction of customary closing conditions, including the tender of a majority of the outstanding shares of Turning Point’s common stock and the receipt of applicable regulatory approvals. In July, the Company announced that the tender offer period was extended to August 15. The acquisition is expected to close during the third quarter of 2022.
In June, the company and Immatics N.V. (NASDAQ: IMTX) announced that they have expanded their strategic alliance to pursue the development of multiple allogeneic off-the-shelf TCR-T and/or CAR-T programs. (link)
Environmental, Social & Governance (ESG)

As a leading biopharma company, we understand our responsibility extends well beyond the discovery, development, and delivery of innovative medicines. Our evolving Environmental, Social, and Governance (ESG) strategy builds on a legacy of comprehensive and global sustainability efforts. To learn more about our priorities and goals, please visit our latest ESG report.

The company announced that its Board of Directors elected Deepak L. Bhatt, MD, MPH to the Board, effective June 14, 2022 and that he will serve as a member of the Science & Technology Committee of the Board of Directors. The size of the Board was increased to eleven in connection with the election of Dr. Bhatt. (link)
In July, the company, in collaboration with Disability Solutions, announced the launch of the Disability Diversity in Clinical Trials (DDiCT) initiative that aims to improve clinical trial participation of people with disabilities to ensure all patient groups are reflective of the real-world population and aligned with the epidemiology of the disease studies. (link)
Financial Guidance

Bristol Myers Squibb is adjusting its 2022 GAAP and non-GAAP line-item guidance as follows:

Total Sales and In-Line Products & New Product Portfolio sales are being adjusted to account for foreign exchange impacts.

Non-GAAP gross margin is being increased to approximately 79% primarily due to foreign exchange impacts.

Adjusting GAAP EPS guidance primarily due to changes in fair market value of equity investments and reaffirming non-GAAP EPS guidance.

Key 2022 GAAP and non-GAAP line-item guidance assumptions are:

No change

1 Key LOE Products = Revlimid and Abraxane
2 Operating Expenses = MS&A and R&D, excluding acquired IPRD and Amortization of acquired intangibles
3 April guidance includes net impact of ($0.21) from acquired IPRD and licensing income, which comprises ($0.10) in Q1 and an additional ($0.11) in April due to buyout of future royalty obligation; July guidance includes YTD net impact of ($0.24) from acquired IPRD and licensing income

The 2022 financial guidance excludes the impact of any potential future strategic acquisitions and divestitures, and any specified items that have not yet been identified and quantified and impact of future Acquired IPRD and charges that may result from the acquisition of Turning Point. Both GAAP and non-GAAP guidance assume current exchange rates. The 2022 non-GAAP EPS guidance is further explained under "Use of Non-GAAP Financial Information." The financial guidance is subject to risks and uncertainties applicable to all forward-looking statements as described elsewhere in this press release.

Conference Call Information

Bristol Myers Squibb will host a conference call today at 8 a.m. EDT during which company executives will review the quarterly financial results and address inquiries from investors and analysts.

Investors and the general public are invited to listen to a live webcast of the call at View Source." target="_blank" title="View Source." rel="nofollow">View Source To be directly connected to the conference call, enter your information here; the link will be active 15 minutes prior to the scheduled start time of the call, and does not require a dial-in number or operator assistance to be connected. Investors and the public can also access the live webcast by dialing in the U.S. toll free 888-300-0211 or international +1 786-460-7199, confirmation code: 6873379. Materials related to the call will be available at View Source prior to the start of the conference call.

A replay of the webcast will be available on View Source approximately three hours after the conference call concludes. A replay of the conference call will be available beginning at 11:30 a.m. EDT on July 27 through 11:30 a.m. EDT on August 10, 2022, by dialing in the U.S. toll free 888-203-1112 or international +1 719-457-0820, confirmation code: 6873379.

ADC Therapeutics Doses First Patient in Phase 1b Clinical Trial of ADCT-601 Targeting AXL as a Single Agent and in Combination with Gemcitabine in Advanced Solid Tumors

On July 27, 2022 ADC Therapeutics SA (NYSE: ADCT) reported the first patient has been dosed in the Phase 1b clinical trial evaluating ADCT-601 (mipasetamab uzoptirine) targeting AXL as a single agent and in combination with gemcitabine in patients with selected advanced solid tumors (Press release, ADC Therapeutics, JUL 27, 2022, View Source [SID1234616981]).

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The Phase 1b open-label, dose-escalation and dose-expansion clinical trial evaluates the safety and tolerability of ADCT-601 as a single agent and in combination with gemcitabine in patients with selected advanced solid tumors. The first arm of the trial will enroll approximately 18 patients with sarcoma, a tumor resistant to current available cancer treatments in which AXL is overexpressed. For more information about the Phase 1b trial, please visit www.clinicaltrials.gov (identifier NCT05389462).

About ADCT-601

ADCT-601 is composed of a humanized monoclonal antibody that binds to human AXL (licensed from BerGenBio), conjugated using GlycoConnect technology (licensed from Synaffix BV) to a linker with a pyrrolobenzodiazepine (PBD)-dimer toxin. Once bound to an AXL-expressing cell, ADCT-601 is internalized into the cell, where enzymes release the PBD-based warhead. In preclinical human cancer models via AXL-mediated delivery of a PBD dimer warhead, ADCT-601 demonstrated potent and durable antitumor activity.

Aptose to Present at the Canaccord Genuity 42nd Annual Growth Conference

On July 27, 2022 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral kinase inhibitors to treat hematologic malignancies, reported that Dr. William G. Rice, Chairman, President and CEO of Aptose, and Mr. Fletcher Payne, CFO of Aptose, will attend the Canaccord Genuity 42nd Annual Growth Conference, and Dr. Rice will present at the Conference (Press release, Aptose Biosciences, JUL 27, 2022, View Source [SID1234616979]):

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Canaccord Genuity 42nd Annual Growth Conference

Date: Wednesday, August 10, 2022
Time: 3:30 p.m. ET
Webcast: Link
The Aptose management team also will be hosting 1×1 meetings during the events.

United Therapeutics Corporation to Report Second Quarter 2022 Financial Results Before the Market Opens on Wednesday, August 3, 2022

On July 27, 2022 United Therapeutics Corporation (Nasdaq: UTHR) reported that it will report its second quarter 2022 financial results before the market opens on Wednesday, August 3, 2022 (Press release, United Therapeutics, JUL 27, 2022, View Source [SID1234616978]).

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United Therapeutics will host a public webcast Wednesday, August 3, 2022, at 9:00 a.m. Eastern Time. The webcast will be accessible via United Therapeutics’ website at View Source A rebroadcast of the webcast will be available for one week and can be accessed at the same location.