On August 15, 2022 Gilead Sciences, Inc. (Nasdaq: GILD) reported an agreement with Everest Medicines to transfer all development and commercialization rights to Gilead for Trodelvy (sacituzumab govitecan) in Greater China, South Korea, Singapore, Indonesia, Philippines, Vietnam, Thailand, Malaysia and Mongolia (Press release, Gilead Sciences, AUG 15, 2022, View Source [SID1234618386]).

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In China mainland and Singapore, Trodelvy is approved for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. Gilead continues to work closely with regulatory bodies in Hong Kong, South Korea and Taiwan, where New Drug Applications, filed by Everest Medicines for metastatic TNBC, are currently under review.

"Trodelvy is approved for second-line metastatic TNBC in over 35 countries. We thank Everest Medicines for their partnership and important contributions in the development of Trodelvy in Asia. Their collaboration has brought us closer to bringing Trodelvy to patients who need alternative options," said Bill Grossman, MD, PhD, Senior Vice President, Oncology Clinical Research, Gilead Sciences. "Trodelvy is the cornerstone of our solid tumor portfolio, and we are committed to bringing this transformative therapy to as many patients as possible. We look forward to rapidly advancing our development program in Asia and to realizing the clinical potential of Trodelvy across diverse tumor types."

In April 2019, Everest Medicines and Immunomedics entered into an agreement granting Everest Medicines an exclusive license to develop and commercialize Trodelvy in Greater China, South Korea, Singapore, Indonesia, Philippines, Vietnam, Thailand, Malaysia and Mongolia, excluding Japan. Gilead subsequently acquired Immunomedics in October 2020 and created an extensive global clinical development program, including investigating Trodelvy as a monotherapy and in novel combinations, across multiple disease areas including non-small cell lung cancer, metastatic urothelial cancer and gastrointestinal cancers.

"We welcome the opportunity to restructure our partnership with Gilead, which has been built on a shared vision of providing innovative oncology solutions for patients in need. With capital resources and a track record of successful therapeutic development and commercialization for Trodelvy in the U.S., Gilead is an ideal partner to further develop and commercialize Trodelvy in Asia Pacific regions to maximize patient access," said Kerry Blanchard, MD, PhD, Chief Executive Officer of Everest Medicines. "I am exceedingly proud of what Everest has accomplished in advancing Trodelvy in China and other Asia territories, and we will continue to bring more transformational therapies to patients in China and worldwide with our extensive pipeline of clinical and pre-clinical stage assets."

Under the terms of the agreement, Gilead will make a $280 million upfront payment to Everest. In addition, Everest is eligible to receive up to $175 million in potential additional payments upon achievement of certain regulatory and commercial milestones. Gilead will also have the opportunity to recruit Everest employees working directly on the Trodelvy program. The transaction is expected to close later this year, and will be subject to customary closing conditions, including approval by Everest’s shareholders.

Trodelvy U.S. Prescribing Information has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; see below for Important Safety Information.

About Trodelvy

Trodelvy (sacituzumab govitecan-hziy) is a first-in-class Trop-2 directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and bladder cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the microenvironment.

Trodelvy is approved in over 35 countries, with multiple additional regulatory reviews underway worldwide, for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. Trodelvy is also approved in the U.S. under the accelerated approval pathway for the treatment of adult patients with locally advanced or metastatic urothelial cancer (UC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.

Trodelvy is also being developed for potential investigational use in other TNBC and metastatic UC populations, as well as a range of tumor types where Trop-2 is highly expressed, including hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer, metastatic non-small cell lung cancer (NSCLC), metastatic small cell lung cancer (SCLC), head and neck cancer, and endometrial cancer.

U.S. Indications for Trodelvy

In the United States, Trodelvy is indicated for the treatment of:

Adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Adult patients with locally advanced or metastatic UC who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
U.S. Important Safety Information for Trodelvy

BOXED WARNING: NEUTROPENIA AND DIARRHEA

Severe or life-threatening neutropenia may occur. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay.
Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. Administer atropine, if not contraindicated, for early diarrhea of any severity. At the onset of late diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold Trodelvy until resolved to ≤Grade 1 and reduce subsequent doses.
CONTRAINDICATIONS

Severe hypersensitivity reaction to Trodelvy.
WARNINGS AND PRECAUTIONS

Neutropenia: Severe, life-threatening, or fatal neutropenia can occur and may require dose modification. Neutropenia occurred in 61% of patients treated with Trodelvy. Grade 3-4 neutropenia occurred in 47% of patients. Febrile neutropenia occurred in 7%. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 on Day 1 of any cycle or neutrophil count below 1000/mm3 on Day 8 of any cycle. Withhold Trodelvy for neutropenic fever.

Diarrhea: Diarrhea occurred in 65% of all patients treated with Trodelvy. Grade 3-4 diarrhea occurred in 12% of patients. One patient had intestinal perforation following diarrhea. Neutropenic colitis occurred in 0.5% of patients. Withhold Trodelvy for Grade 3-4 diarrhea and resume when resolved to ≤Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments.

Hypersensitivity and Infusion-Related Reactions: Serious hypersensitivity reactions including life-threatening anaphylactic reactions have occurred with Trodelvy. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 37% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of Trodelvy was 0.3%. The incidence of anaphylactic reactions was 0.3%. Pre-infusion medication is recommended. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Medication to treat such reactions, as well as emergency equipment, should be available for immediate use. Permanently discontinue Trodelvy for Grade 4 infusion-related reactions.

Nausea and Vomiting: Nausea occurred in 66% of all patients treated with Trodelvy and Grade 3 nausea occurred in 4% of these patients. Vomiting occurred in 39% of patients and Grade 3-4 vomiting occurred in 3% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold Trodelvy doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with Trodelvy. The incidence of Grade 3-4 neutropenia was 67% in patients homozygous for the UGT1A1*28, 46% in patients heterozygous for the UGT1A1*28 allele and 46% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 25% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 11% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue Trodelvy based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function.

Embryo-Fetal Toxicity: Based on its mechanism of action, Trodelvy can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. Trodelvy contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Trodelvy and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Trodelvy and for 3 months after the last dose.

ADVERSE REACTIONS

In the ASCENT study (IMMU-132-05), the most common adverse reactions (incidence ≥25%) were fatigue, neutropenia, diarrhea, nausea, alopecia, anemia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes.

In the TROPHY study (IMMU-132-06), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, neutropenia, nausea, any infection, alopecia, anemia, decreased appetite, constipation, vomiting, abdominal pain, and rash. The most frequent serious adverse reactions (SAR) (≥5%) were infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), and sepsis or bacteremia (5%). SAR were reported in 44% of patients, and 10% discontinued due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPHY study were reduced neutrophils, leukocytes, and lymphocytes.

DRUG INTERACTIONS

UGT1A1 Inhibitors: Concomitant administration of Trodelvy with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with Trodelvy.

UGT1A1 Inducers: Exposure to SN-38 may be substantially reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with Trodelvy.

On August 15, 2022 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) for Polivy (polatuzumab vedotin-piiq) in combination with Rituxan (rituximab) plus cyclophosphamide, doxorubicin and prednisone (R-CHP) for the treatment of people with previously untreated diffuse large B-cell lymphoma (DLBCL) (Press release, Genentech, AUG 15, 2022, View Source [SID1234618385]). The FDA is expected to make a decision on approval by April 2, 2023.

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"The POLARIX study results suggest that Polivy plus R-CHP could transform the treatment of this aggressive malignancy, and we are working with the FDA to bring this combination to newly diagnosed DLBCL patients as soon as possible," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "We hope it will become the new standard of care for the first-line treatment of DLBCL, potentially reducing the need for subsequent treatments and limiting patient burden."

DLBCL is an aggressive blood cancer. Although DLBCL often responds to initial treatment, it is not cured with the current standard of care in four out of 10 people. Most relapses occur within two years of starting treatment, and the majority of those who require subsequent lines of therapy have poor outcomes.

The sBLA is based on results from the pivotal Phase III POLARIX trial, which is the first in two decades to show a clinically meaningful improvement in progression-free survival (PFS) compared to the current standard of care Rituxan plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). The risk of disease progression, relapse or death was reduced by 27% with Polivy plus R-CHP compared with R-CHOP after a median follow-up of 28.2 months (hazard ratio [HR] 0.73; 95% confidence interval [CI]: 0.57–0.95; p<0.02). Safety outcomes were consistent with those seen in previous clinical trials, and the safety profile was comparable for Polivy plus R-CHP versus R-CHOP, including rates of Grade 3-4 adverse events (AEs; 57.7% versus 57.5%), serious AEs (34.0% versus 30.6%), Grade 5 AEs (3.0% versus 2.3%), and AEs leading to dose reduction (9.2% versus 13.0%).

Based on pivotal data from the POLARIX study, the European Commission approved Polivy in combination with R-CHP in May 2022 for the treatment of adult patients with previously untreated DLBCL. Polivy is currently approved as a readily available, fixed-duration treatment option for relapsed or refractory (R/R) DLBCL in combination with bendamustine and Rituxan/Mabthera in more than 70 countries worldwide, including in the United States and in the EU.

Genentech continues to explore areas of unmet need where Polivy has the potential to deliver additional benefit, including in ongoing studies investigating combinations of Polivy with the company’s CD20xCD3 T-cell engaging bispecific antibodies mosunetuzumab and glofitamab, and with Rituxan in combination with gemcitabine and oxaliplatin in the Phase III POLARGO study.

About the POLARIX Study

POLARIX [NCT03274492] is an international Phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of Polivy (polatuzumab vedotin-piiq) plus Rituxan (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) versus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in people with previously untreated diffuse large B-cell lymphoma (DLBCL). Eight-hundred and seventy-nine patients were randomized 1:1 to receive either Polivy plus R-CHP plus a vincristine placebo for six cycles, followed by rituximab for two cycles; or R-CHOP plus a Polivy placebo for six cycles, followed by two cycles of rituximab. The primary outcome measure is progression-free survival (PFS) as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma. POLARIX is being conducted in collaboration with The Lymphoma Study Association (LYSA) and The Lymphoma Academic Research Organisation (LYSARC). Other clinical investigators from around the world also participated in the trial.

About Diffuse Large B-cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin’s lymphoma (NHL), accounting for about one in three cases of NHL. DLBCL is an aggressive (fast-growing) type of NHL. While it is generally responsive to treatment in the frontline, as many as 40% of people will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short. Approximately 150,000 people worldwide are estimated to be diagnosed with DLBCL each year.

About Polivy (polatuzumab vedotin-piiq)

Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B cells, an immune cell impacted in some types of non-Hodgkin’s lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to cancer cells such as CD79b and destroys these B cells through the delivery of an anti-cancer agent, which is thought to minimize the effects on normal cells. Polivy is being developed by Genentech using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL.

Polivy U.S. Indication

Polivy is a prescription medicine used with other medicines, bendamustine and a rituximab product, to treat diffuse large B-cell lymphoma in adults who have progressed after at least two prior therapies.

The accelerated approval of Polivy is based on a type of response rate. There are ongoing studies to confirm the clinical benefit of Polivy.

Important Safety Information

Possible serious side effects

Everyone reacts differently to Polivy therapy, so it’s important to know what the side effects are. Some people who have been treated with Polivy have experienced serious to fatal side effects. A patient’s doctor may stop or adjust a patient’s treatment if any serious side effects occur. Patients must contact their healthcare team if there are any signs of these side effects.

Nerve problems in arms and legs: This may happen as early as after the first dose and may worsen with every dose. If a patient already has nerve pain, Polivy may make it worse. The patient’s doctor will monitor for signs and symptoms, such as changes in sense of touch, numbness or tingling in hands or feet, nerve pain, burning sensation, any muscle weakness, or changes to walking patterns
Infusion-related reactions: A patient may experience fever, chills, rash, breathing problems, low blood pressure, or hives within 24 hours of the infusion
Infections: Patients should contact their healthcare team if they experience a fever of 100.4°F or higher, chills, cough, or pain during urination. Also, a patient’s doctor may give medication before giving Polivy, which may prevent some infections, and monitor blood counts throughout treatment with Polivy. Treatment with Polivy can cause severe low blood cell counts
Rare and serious brain infections: A patient’s doctor will monitor the patient closely for signs and symptoms of these types of infections. Patients should contact their doctor if they experience confusion, dizziness or loss of balance, trouble talking or walking, or vision changes
Tumor lysis syndrome: Caused by the fast breakdown of cancer cells. Signs include nausea, vomiting, diarrhea, and lack of energy
Potential harm to liver: Some signs include tiredness, weight loss, pain in the abdomen, dark urine, and yellowing of the skin or the white part of the eyes. Patients may be at higher risk if they already have liver problems or are taking other medication
Side effects seen most often

The most common side effects during treatment were:

Low blood cell counts (platelets, red blood cells, white blood cells)
Nerve problems in arms and legs
Tiredness or lack of energy
Diarrhea
Nausea
Fever
Decreased appetite
Infections
Polivy may not be for everyone. A patient should talk to their doctor if they are:

Pregnant or may be pregnant: Data have shown that Polivy may harm an unborn baby
Planning to become pregnant: Women should avoid getting pregnant while taking Polivy. Women should use effective contraception during treatment and for at least 3 months after their last Polivy treatment. Men taking Polivy should use effective contraception during treatment and for at least 5 months after their last Polivy treatment
Breastfeeding: Women should not breastfeed while taking Polivy and for at least 2 months after the last dose
These may not be all the side effects. Patients should talk to their healthcare provider for more information about the benefits and risks of Polivy treatment.

Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Please visit View Source for the full Prescribing Information for additional Important Safety Information.

About Genentech in Hematology

For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. For more information visit View Source

On August 15, 2022 ADC Therapeutics SA (NYSE: ADCT) reported that it has completed a series of strategic transactions in which it (Press release, ADC Therapeutics, AUG 15, 2022, View Source [SID1234618384]):

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Entered into a new $175 million senior secured term loan with certain funds of Owl Rock, a division of Blue Owl Capital, Inc. ("Owl Rock"), and funds managed by Oaktree Capital Management, L.P. ("Oaktree") with an upfront tranche of $120 million received upon closing today;
Settled in full the $115 million aggregate principal amount of senior secured convertible notes held by Deerfield Management Company ("Deerfield") due May 2025 for (i) $117.3 million in cash including the contractual exit fee on principal repayment, (ii) 2,390,297 common shares approximately equal to the value of the remaining interest due on the convertible debenture to the end of term, and (iii) warrants to purchase an aggregate of 4,412,840 common shares at exercise prices of $24.70 and $28.07 per share;
Entered into a share purchase agreement with certain funds of Owl Rock, a division of Blue Owl Capital Inc., for an investment of $6.25 million for 733,568 common shares.
"We are pleased to enter into this agreement with Owl Rock and Oaktree, the proceeds of which will be used to pay the cash consideration in the exchange of the secured convertible credit notes held by Deerfield," said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. "This new debt facility has a term of seven years and enables us to continue maximizing the potential of ZYNLONTA and advancing our pipeline of novel antibody drug conjugates for hematologic malignancies and solid tumors. The continued equity support of Deerfield and the additional equity support from Owl Rock is also very positive, and we are pleased to maintain our cash runway into early 2025 as this deal is approximately cash neutral during that timeframe."

Pursuant to the loan and guaranty agreement, the Company completed an initial drawdown of $120 million on August 15, 2022. This amount was used by the Company to fund the cash consideration as part of the settlement of Deerfield’s senior secured convertible notes. Up to two additional tranches in the amount of $27.5 million each can be drawn by the Company upon meeting certain conditions within 18 months. The term loan matures on August 15, 2029 and accrues interest at an annual rate of secured overall financing rate (SOFR) plus 7.50% or a base rate plus 6.50% for the first five years of the term loans and at an annual rate of SOFR plus 9.25% or a base rate plus 8.25% thereafter. In addition, the Company issued to the lenders under the term loan warrants to purchase an aggregate number of common shares equal to $4.375 million divided by the volume weighted-average price of the common shares for the ten trading days prior to their issuance and the ten trading days on and after their issuance, which warrants are exercisable for ten years from their issuance.

Owl Rock also agreed to purchase 733,568 common shares for $8.52 per share, which represents the 5-day volume-weighted average price as of Friday, August 12, 2022. The transaction is expected to close upon registration of the necessary share capital increase with the commercial register in Switzerland.

Sandip Agarwala, Managing Director with Owl Rock commented, "This transaction displays our ability to integrate our life sciences sector expertise and tailored multi-security approach to help provide growth capital to companies like ADC Therapeutics. We are pleased to invest in ADC Therapeutics’ strong team, portfolio and track record of success in developing and commercializing life-saving cancer therapies including ZYNLONTA."

"We are excited to partner with ADC Therapeutics as it continues to develop a pipeline of novel ADCs for hematologic malignancies and solid tumors," said Aman Kumar, Co-Portfolio Manager of Life Sciences Lending at Oaktree. "This is an important time in the Company’s development with its first product approval validating its first-in-class ADC platform. This commitment of capital represents our belief in the long-term potential of ADC Therapeutics and we look forward to working with the Company’s leadership team during this next phase of growth."

Elise Wang, Partner, Head of Private Equity Capital Markets at Deerfield said: "We have been a supporter of ADC Therapeutics dating back to its successful IPO in May 2020 as both an equity investor in the IPO and also providing the convertible debenture that is being retired today. We are very pleased to take a significant portion of the repayment consideration in ADCT stock and look forward to continuing to support the company going forward."

The transactions described herein are further described in a Report on Form 6-K filed today with the Securities and Exchange Commission. The descriptions herein are qualified in their entirety by reference to the further descriptions included in the Report on Form 6-K.

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

Morgan Stanley & Co. LLC acted as the sole placement agent to ADC Therapeutics on this transaction.

On August 15, 2022 Guardant Health Inc. (Nasdaq: GH), a leading precision oncology company, reported that Guardant Reveal, the only tissue-free test for the detection of residual and recurrent disease for colorectal cancer (CRC), is now available for patients with breast and lung cancers (Press release, Guardant Health, AUG 15, 2022, View Source [SID1234618382]).

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The Guardant Reveal blood test improves the management of early-stage cancer patients by detecting circulating tumor DNA (ctDNA) in blood after surgery—without the need for a tissue biopsy—to identify patients with minimal residual disease (MRD) who have a higher risk for recurrence and may benefit from additional therapy. The test has also been shown to predict disease recurrence more effectively than current standard-of-care tools, like carcinoembryonic antigen (CEA) tests, which are limited in their ability to identify patients at high risk for recurrence.2

"We are very pleased to be able to make the Guardant Reveal test available to patients with breast and lung cancer, where obtaining a tissue biopsy can be a challenge," said Helmy Eltoukhy, Guardant Health co-CEO. "With a simple blood draw, this test allows oncologists to confidently assess risk for their breast and lung cancer patients so they can quickly identify those patients who may benefit from therapy after surgery, as well as detect cancer recurrence earlier."

The Guardant Reveal test may be initiated as soon as three weeks after surgery. For more information, visit guardantreveal.com.

About Guardant Reveal

Guardant Reveal is the first blood-only test that detects residual and recurrent disease in patients with Stage II and III CRC, breast or lung cancer without the need for a tissue biopsy. Combining genomic and epigenomic signals, the test detects ctDNA in blood after surgery to identify patients with residual disease who may benefit most from adjuvant therapy, and to monitor for recurrence of disease in previously diagnosed patients.

On August 15, 2022 Gamida Cell Ltd. (Nasdaq: GMDA), the leader in the development of NAM-enabled cell therapies for patients with hematologic and solid cancers and other serious diseases, reported financial results for the quarter ended June 30, 2022 (Press release, Gamida Cell, AUG 15, 2022, View Source [SID1234618381]). Net loss for the second quarter of 2022 was $18.6 million, compared to a net loss of $23.6 million in the second quarter of 2021. As of June 30, 2022, Gamida Cell had total cash, cash equivalents and investments of $55.1 million.

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Recently, Gamida Cell:

Received acceptance for filing from the U.S. Food and Drug Administration (FDA) with priority review for its Biologics License Application (BLA) for omidubicel. The BLA has been assigned a Prescription Drug User Fee Act (PDUFA) target action date of January 30, 2023. If approved, omidubicel will be the first allogeneic advanced stem cell therapy donor source for patients with blood cancers in need of a stem cell transplant.
Dosed the first patient in a company-sponsored Phase 1/2 study evaluating a cryopreserved formulation of GDA-201, a readily available cell therapy candidate for the treatment of follicular and diffuse large B-cell lymphomas.
Continued development of the company’s proprietary NAM-enabled NK cell pipeline, including genetically modified product candidates GDA-301, GDA-401, GDA-501 and GDA-601, which aim to treat solid-tumor and hematological cancers. These cell therapy candidates utilize CAR, membrane bound- and CRISPR-mediated technologies to increase the NK cell targeting, potency and persistence against hematologic malignancies and solid tumors. Promising new pre-clinical data on GDA-301 and GDA-601 were presented at the International Society for Cell & Gene Therapy Meeting. The data demonstrated that both NAM-enabled cell therapy candidates represented a novel potent and cytotoxic approach in fighting cancer.
Advanced strategic evaluation for omidubicel commercialization, including assessing whether to commercialize omidubicel ourselves or to pursue strategic alternatives to commercialize omidubicel, upon receipt of regulatory approval. The company currently has sufficient cash to fund the company’s operations into mid-2023, excluding the cost of commercializing omidubicel.
"2022 is a potentially transformative year for Gamida Cell as we continue to execute against our clinical and regulatory milestones. We were excited that the FDA accepted our BLA submission with priority review, and if approved, omidubicel will be the first allogeneic advanced stem cell therapy donor source for patients with blood cancers in need of a stem cell transplant. We believe that omidubicel has the potential to change the outlook for patients suffering from blood cancers through improved outcomes, quality of life and increased access for patients who are currently eligible for transplant, but cannot find a match," said Julian Adams, Ph.D., chief executive officer of Gamida Cell. "In addition, the development of our NAM-enabled NK cell therapy candidate, GDA-201, creates an opportunity to potentially bring a new treatment option to tens of thousands of patients with relapsed/refractory lymphoma worldwide. We continue to execute our mission of advancing our broad pipeline of NAM-enabled cell therapies with a curative approach for patients with solid tumors and blood cancers and other serious blood diseases."

Second Quarter and Recent Developments

Omidubicel: Advanced Cell Therapy

BLA accepted by FDA with Priority Review: In August 2022, the FDA accepted for filing Gamida Cell’s BLA for omidubicel for the treatment of patients with blood cancers in need of an allogeneic hematopoietic stem cell transplant. The FDA granted Priority Review for the BLA and has set a PDUFA target action date of January 30, 2023. In parallel, Gamida Cell is preparing for the commercialization of omidubicel in the U.S.
GDA-201: NAM-Enabled NK Cell Therapy

Dosed the first patient in Phase 1/2 study of cryopreserved formulation of GDA-201: In August 2022, Gamida Cell completed the dosing of the first patient in a company-sponsored Phase 1/2 study evaluating a cryopreserved formulation of GDA-201 for the treatment of follicular and diffuse B-cell lymphomas.
The Phase 1 portion of the study is designed as a dose escalation phase to evaluate the safety of GDA-201, and will include patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL)/high grade B-cell lymphoma (HGBCL), marginal zone lymphoma or mantle cell lymphoma. The Phase 2 expansion phase is designed to evaluate the safety and efficacy of GDA-201 in 63 patients comprised of two patient cohorts, FL and DLBCL. The study will include patients who have relapsed or refractory lymphoma after at least two prior treatments, which may include CAR-T or stem cell transplant.
NAM-Enabled NK Cell Pipeline Expansion

Progressed NAM-enabled genetically modified NK pipeline: Gamida Cell continues to progress its NAM-enabled genetically modified NK pipeline, which utilizes CAR, membrane bound- and CRISPR-mediated technologies to increase targeting, potency and persistence against hematologic malignancies and solid tumors. The company continues to conduct in vitro and in vivo preclinical proof-of-concept studies for these genetically modified NK therapeutic targets which are already showing encouraging results and plans to select the next NK pipeline product candidate for IND enabling studies by the end of 2022. These therapeutic targets include:
GDA-301: Knockout of CISH (cytokine inducible SH2 containing protein) in NK cells using CRISPR/Cas9 in combination with a membrane-bound IL-15/IL-15Ra;
GDA-401: A development candidate with an undisclosed target;
GDA-501: Anti HER2 CAR-engineered NK cells to target solid tumors expressing HER2, based on a single-chain variable fragment of the widely used humanized monoclonal antibody trastuzumab; and
GDA-601: CRISPR Knockout of CD38 on NK cells combined with anti CD38 CAR. CD38 is an established immunotherapeutic target in multiple myeloma, but its expression on NK cells and its further induction during ex vivo NK cell expansion represents a barrier to the development of an anti CD38 CAR-NK cell therapy. Gamida Cell is advancing this program in collaboration with the Dana-Farber Cancer Institute to study the in vitro cytotoxicity of GDA-601 in fresh tumor tissue samples from multiple myeloma patients.
Corporate Updates

Appointed Ivan M. Borrello, M.D. to Board of Directors: Dr. Borrello is an Associate Professor of Oncology at the Sydney Kimmel Comprehensive Cancer Center at Johns Hopkins and a renowned physician and author who has made major contributions to better the understanding of immunotherapies and the treatment of hematologic malignancies as well as bone marrow transplant. The Company also announced the resignation of Ofer Gonen from its Board of Directors.
Second Quarter 2022 Financial Results

Research and development expenses were $10.6 million in the second quarter of 2022, compared to $13.4 million in the same quarter in 2021. The decrease was attributable mainly to a $2.4 million decrease in clinical activities relating to the conclusion of our Phase 3 clinical trial and a decrease of $0.4 million in the GDA-201 clinical program.
Commercial expenses were $3.2 million in the second quarter of 2022, compared to $5.0 million in the second quarter of 2021. The decrease was attributable mainly to reducing near-term commercial readiness expenses, as we continued to assess strategic approaches for the commercialization of omidubicel.
General and administrative expenses were $4.3 million in the second quarter of 2022, compared to $3.9 million in the same period in 2021. The increase was mainly due to a $0.9 million increase in professional services expenses, offset by a decrease of $0.5 million in headcount related expenses.
Finance expenses, net, were $0.5 million in the second quarter of 2022, compared to $1.3 million in the same period in 2021. The decrease was primarily due to $0.6 million in non-cash expenses and an increase of $0.2 million in interest income from cash management.
Net loss was $18.6 million in the second quarter of 2022, compared to a net loss of $23.6 million in the second quarter of 2021.
2022 Financial Guidance

Gamida Cell expects that its current cash, cash equivalents and investments will support the company’s ongoing operating activities into mid 2023, excluding the cost of commercializing omidubicel. If we decide to market omidubicel ourselves, we will require substantial additional funding. This cash runaway guidance is based on the company’s current operational plans and excludes any additional funding and any business development activities that may be undertaken. Gamida Cell continues to assess all financing options that support its corporate strategy.

Expected Milestones in 2022 and Early 2023

Omidubicel

PDUFA target action date of January 30, 2023.
NK cell pipeline expansion

Conduct preclinical proof of concept studies of the NAM-enabled, genetically modified NK therapeutic targets
Select pipeline candidate for IND-enabling studies
Conference Call Information

Gamida Cell will host a conference call today, August 15, 2022, at 8:00 a.m. ET to discuss these financial results and company updates. To access the conference call, please register here and be advised to do so at least 10 minutes prior to joining the call. A live webcast of the conference call can be accessed in the "Investors & Media" section of Gamida Cell’s website at www.gamida-cell.com. A replay of the webcast will be available approximately two hours after the event, for approximately 30 days.

About Omidubicel

Omidubicel is an advanced cell therapy candidate developed as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant for patients with blood cancers. Omidubicel demonstrated a statistically significant reduction in time to neutrophil engraftment in comparison to standard umbilical cord blood in an international, multi-center, randomized Phase 3 study (NCT0273029) in patients with hematologic malignancies undergoing allogeneic bone marrow transplant. The Phase 3 study also showed reduced time to platelet engraftment, reduced infections and fewer days of hospitalization. One-year post-transplant data showed sustained clinical benefits with omidubicel as demonstrated by significant reduction in infectious complications as well as reduced non-relapse mortality and no significant increase in relapse rates nor increases in graft-versus-host-disease (GvHD) rates. Omidubicel is the first stem cell transplant donor source to receive Breakthrough Therapy Designation from the FDA and has also received Orphan Drug Designation in the US and EU.

Omidubicel is an investigational stem cell therapy candidate, and its safety and efficacy have not been established by the FDA or any other health authority. For more information about omidubicel, please visit View Source

About GDA-201

Gamida Cell applied the capabilities of its nicotinamide (NAM)-enabled cell expansion technology to develop GDA-201, an innate NK cell immunotherapy candidate for the potential treatment of hematologic and solid tumors in combination with standard of care antibody therapies. GDA-201, the lead candidate in the NAM-enabled NK cell pipeline, has demonstrated promising initial clinical study data. Preclinical studies have shown that GDA-201 may address key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs. Furthermore, these data suggest GDA-201 may improve antibody-dependent cellular cytotoxicity (ADCC) and tumor targeting of NK cells. There are approximately 40,000 patients with relapsed/refractory lymphoma in the US and EU, which is the patient population that will be studied in the currently ongoing GDA-201 Phase 1/2 clinical trial.

For more information about GDA-201, please visit View Source For more information on the Phase 1/2 clinical trial of GDA-201, please visit www.clinicaltrials.gov.

GDA-201 is an investigational cell therapy candidate, and its safety and efficacy have not been established by the FDA or any other health authority.

About NAM Technology

Our NAM-enabling technology, supported by positive omidubicel Phase 3 results, is designed to enhance the number and functionality of targeted cells, enabling us to pursue a curative approach that moves beyond what is possible with existing therapies. Leveraging the unique properties of NAM (nicotinamide), we can expand and metabolically modulate multiple cell types — including stem cells and natural killer cells — with appropriate growth factors to maintain the cells’ active phenotype and enhance potency. Additionally, our NAM technology improves the metabolic fitness of cells, allowing for continued activity throughout the expansion process