On January 30, 2024 CG Oncology, Inc. (Nasdaq: CGON), a late-stage clinical biopharmaceutical company focused on developing and commercializing a potential backbone bladder-sparing therapeutic for patients afflicted with bladder cancer, reported the closing of its upsized initial public offering of 23,000,000 shares of its common stock, which includes the exercise in full by the underwriters of their option to purchase 3,000,000 additional shares, at an initial public offering price of $19.00 per share (Press release, CG Oncology, JAN 30, 2024, View Source [SID1234639730]). All of the shares were offered by CG Oncology. The aggregate gross proceeds from the offering, before deducting underwriting discounts and commissions and other offering expenses, were $437.0 million. CG Oncology’s common stock is listed on the Nasdaq Global Select Market under the ticker symbol "CGON."

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Morgan Stanley, Goldman Sachs & Co. LLC and Cantor acted as joint book-running managers for the offering. LifeSci Capital acted as co-manager for the offering.

Registration statements relating to the offering have been filed with the Securities and Exchange Commission (SEC) and became effective on January 24, 2024. A prospectus relating to and describing the terms of the offering has been filed with the SEC and is available on the SEC’s website at www.sec.gov. The offering was made only by means of a prospectus. Copies of the final prospectus may be obtained from Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, NY 10014, or by email at [email protected]; Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, by telephone at (866) 471-2526, or by email at [email protected]; or Cantor Fitzgerald & Co., Attention: Capital Markets, 110 East 59th Street, 6th Floor, New York, NY 10022, or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any offer or 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 January 30, 2024 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, reported a new study published in The Journal of Thoracic and Cardiovascular Surgery demonstrating the ability of Natera’s personalized and tumor-informed molecular residual disease (MRD) test, Signatera, to risk stratify and detect recurrence early in patients with resected stage I-II non-small cell lung cancer (NSCLC) (Press release, Natera, JAN 30, 2024, View Source [SID1234639729]). The full study can be found here.

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Worldwide, lung cancer is the second most commonly diagnosed cancer. In the U.S., NSCLC accounts for 81% of all lung cancer diagnoses.1 About 25-30% of NSCLC patients are diagnosed with stage I-II disease.2,3 These patients typically undergo curative-intent complete surgical resection and may be treated with adjuvant systemic therapy. However, 30–55% of patients develop disease recurrence within the first five years after surgery, and five-year overall survival ranges from 68-92% for stage I and 53-60% for stage II NSCLC patients respectively.4,5,6

Given the significant risk of recurrence and death in NSCLC, it is critical to accurately risk-stratify patients to identify who may derive benefit from additional treatment after surgery. In addition, there is a need for sensitive and specific biomarkers to support early detection of recurrence before the onset of disease-related symptoms at a time when therapy might provide greater clinical benefit.

This study investigated the association of circulating tumor DNA (ctDNA) status with recurrence-free survival (RFS), as well as changes in clinical practice after a positive ctDNA result in patients with resected stage I-II NSCLC. A total of 378 serial plasma samples from 108 NSCLC patients were analyzed after surgical resection, with a median clinical followup of 16 months.

Key findings include:

Patients who were ctDNA-positive within 6 months post-resection and prior to adjuvant treatment were 53-times more likely to recur (p<0.0001) as compared to ctDNA-negative patients.
ctDNA detection demonstrated a median lead time of 5.5 months when compared to confirmation of recurrence by radiographic imaging.
Post-operative surveillance strategies were altered in 100% of ctDNA-positive patients (earlier radiographic imaging), and patients with PET scans positive for malignant features received early referrals for treatment.
"This study demonstrates that serial monitoring with Signatera can identify patients who are most likely to benefit from adjuvant systemic therapy and/or more intensified imaging," said Minetta Liu, MD, chief medical officer of oncology at Natera. "With measurable clinical impact in 100% of Signatera MRD-positive cases, this study supports the utility of Signatera in the management of non-metastatic, resected NSCLC."

The study builds on previous Signatera data across early- and late-stage NSCLC. This includes a 2023 publication in Frontiers in Oncology, demonstrating Signatera’s ability to risk stratify and detect progression early in unresectable NSCLC,7 as well as the EMPower Lung-1 trial presented at the 2023 ASCO (Free ASCO Whitepaper) annual meeting, which showed Signatera’s ability to monitor response to immunotherapy and predict clinical outcomes in advanced NSCLC patients.8 This recent work also builds upon the 2017 TRACERx Nature publication that first reported Signatera’s ability to detect relapse early with high sensitivity and specificity in patients with resected NSCLC.9

About Signatera

Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard of care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer (stage IIb and higher) and muscle invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 50 peer-reviewed papers.

On January 30, 2024 Agilent Technologies Inc. (NYSE: A) reported an agreement with Incyte that will bring together Agilent’s expertise and proven track record in the development of companion diagnostics (CDx) to support the development and commercialization of Incyte’s hematology and oncology portfolio (Press release, Agilent, JAN 30, 2024, View Source [SID1234639728]).

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The value of the companion diagnostics market is predicted to expand to nearly US $14B by 2030,1 driven in part by the power of these tests to inform treatment decisions for a growing range of cancers and other chronic diseases. Developed for use with targeted therapeutics, companion diagnostics are used to evaluate expression of biomarkers and identify patients that are likely to benefit from treatment with the targeted therapeutic products.

The agreement between Agilent and Incyte allows the companies to collaborate on CDx development programs. This will enable Agilent to continue to expand its companion diagnostics portfolio with novel biomarkers and Incyte to leverage Agilent’s expertise in IVD assay development, global regulatory approvals, and commercialization to support clinical trials as well as the potential registration and commercialization of CDx in the United States and Europe.

Paul Beresford, vice president and general manager of Agilent’s Companion Diagnostics Division, discussed the significance of the partnership: "Leveraging the power of companion diagnostics, we are strategically transforming the treatment paradigm for a broad spectrum of cancers. By working together, Agilent and Incyte hope to expedite the development of innovative precision medicine products, potentially paving the way for enhanced patient health outcomes."

Jeff Jackson, group vice president of Translational Medicine at Incyte added: "Agilent’s expertise in the development of companion diagnostics is impressive, as is their regulatory and commercialization record. We are excited about the collaboration and look forward to working together to innovate in support of patients."

With an established and growing portfolio of world-class chemistries and technologies, Agilent has a strong track record as a provider and partner for companion diagnostics development across the precision oncology sector. This year, Agilent celebrates the 25th anniversary of HercepTest, a critical tool for assessing HER2 expression in breast cancers. Since the launch of HercepTest, Agilent has introduced several additional CDx tests. Among these, the PDL-1 IHC 22C3 franchise has been particularly successful, offering a continually expanding range of tests for assessing PDL-1 expression.

On January 30, 2024 WuXi XDC (2268.HK), a leading global Contract Research, Development and Manufacturing Organization (CRDMO) focused on ADC and the other types of bioconjugate market; and Multitude Therapeutics, a clinical stage biotechnology company renowned for ADC platform technologies, reported that they have reached a comprehensive partnership in drug-linker technology, which is co-developed with HySlink Therapeutics ("HySlink"), and CRDMO services spanning from discovery to commercialization (Press release, Multitude Therapeutics, JAN 30, 2024, View Source [SID1234639726]). WuXi XDC signed a Memorandum of Understanding (MOU) with HySlink on the same day.

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WuXi XDC will provide a fully integrated, one-stop bioconjugate platform and end-to-end CRDMO services. As WuXi XDC’s strategic partner, Multitude Therapeutics will provide proprietary T-Moiety linker technologies, co-developed with HySlink. Both parties will synergize their strengths to build more efficient ADC technology in terms of novel T-moiety linkers, camptothecin derivative conjugation and high DAR value, among others. This platformization of new technologies will enable our clients to accelerate the discovery of preclinical ADC candidates (PCCs) and develop more novel bioconjugates; and improve the development efficiency and rate of success.

Dr. Jimmy Li, CEO of WuXi XDC, commented, "The proprietary drug-linker technology has unique advantages and, when fused with our open-access bioconjugate platform, enables customers to achieve rapid delivery of T-moiety exatecan ADC preclinical candidates, with the potential benefit of expanding the therapeutic window of existing ADC drugs. We are pleased to join hands with Multitude to remain continuously innovative and enhance our technological capabilities to meet our clients’ needs. By leveraging our full range of in-depth industry expertise, we are on the path to creating the world’s leading bioconjugate platform, which empowers the industry, broadly, deeply and fully. "

Multitude and HySlink, stated, "WuXi XDC has exceptional capability as a leading global CRDMO. We are very excited to form a strong alliance in the technical area. Our proprietary new T-Moiety linker can significantly enhance the therapeutic effect of ADCs. The higher stability of the linker and the hydrophilic shielding effect can improve the overall stability of antibody-drug conjugates, extend the drug’s half-life, and potentially overcome multi-drug resistance in tumors. Without increasing side effects, it can further enhance the therapeutic window of existing ADC drugs (related research was published in Cancer Discovery 2023;13(4):950-73). Our collaboration aims to help more ADC developers gain stable and rapid access to these payload linkers, in a bid to benefit patients worldwide."

On January 30, 2024 Johnson & Johnson reported the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking approval of a new indication for DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) in combination with bortezomib, lenalidomide and dexamethasone (D-VRd) for induction and consolidation treatment and with lenalidomide (D-R) for maintenance treatment of adult patients who are newly diagnosed with multiple myeloma (NDMM) and are eligible for autologous stem cell transplant (ASCT) (Press release, Johnson & Johnson, JAN 30, 2024, View Source;johnson-submits-supplemental-biologics-license-application-to-us-fda-seeking-approval-of-darzalex-faspro-daratumumab-and-hyaluronidase-fihj-based-regimen-for-the-treatment-of-patients-with-transplant-eligible-newly-302048440.html [SID1234639725]).

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This submission is supported by data from the Phase 3 PERSEUS (NCT03710603) study evaluating D-VRd induction and consolidation therapy, ASCT, and D-R maintenance therapy, compared to bortezomib, lenalidomide and dexamethasone (VRd), ASCT, and lenalidomide (R) maintenance. Results from the primary analysis showed that the study met its primary endpoint of progression-free survival (PFS), reducing the risk of disease progression or death by 58 percent (Hazard Ratio [HR], 0.42; 95 percent Confidence Interval [CI] 0.30-0.59; P<0.0001).1 Treatment with D-VRd and ASCT followed by D-R maintenance also increased the depth of response with higher rates of complete response (CR) or better, stringent complete response (sCR) and minimal residual disease (MRD) negativity compared to treatment with VRd, ASCT and R maintenance. Overall, 64 percent of patients who entered the maintenance phase in the D-VRd arm were able to discontinue treatment with DARZALEX FASPRO after achieving a complete response or better and sustained MRD-negativity following at least two years of D-R maintenance in accordance with the protocol. The overall safety profile of D-VRd followed by D-R maintenance was consistent with the known safety profiles for DARZALEX FASPRO, VRd and R.

"We are committed to changing the course of multiple myeloma through building combination regimens such as D-VRd with complementary mechanisms of action. The DARZALEX FASPRO-based quadruplet therapy demonstrated a clinically significant reduction in the risk of progression or death for transplant-eligible, newly diagnosed patients with multiple myeloma," said Craig Tendler, M.D., Vice President, Clinical Development, Diagnostics, and Global Medical Affairs, Johnson & Johnson Innovative Medicine. "Patients are most likely to experience their deepest and most durable responses during the first line of treatment with D-VRd. This regimen has the potential to improve long-term outcomes for newly diagnosed patients and we look forward to working with the FDA on the review of this application."

Data from the PERSEUS study were presented as a late-breaking oral presentation (LBA–1) at the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and simultaneously published in The New England Journal of Medicine.

About the PERSEUS study

The PERSEUS study is being conducted in collaboration with the European Myeloma Network as the sponsor. PERSEUS is an ongoing, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd and ASCT followed by D-R maintenance vs VRd and ASCT followed by R maintenance in patients with transplant-eligible NDMM. The primary endpoint is PFS, and secondary endpoints include overall CR or better rate, overall MRD-negativity (in patients with CR or better), and overall survival. DARZALEX FASPRO was discontinued after at least 24 months of D-R maintenance therapy in patients who had a CR or better and had sustained MRD–negative status for at least 12 months. The median age is 61.0 (range, 32-70) years for patients in the D-VRd arm and 59.0 (range, 31-70) years for patients in the VRd arm. The study is being conducted in 14 countries in Europe and Australia.

About multiple myeloma

Multiple myeloma is a blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.2 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.3 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.4 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease.5 People with multiple myeloma have a 5-year survival rate of 59.8 percent.5 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.6,7

About DARZALEX FASPRO

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for eight indications in multiple myeloma, three of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.8 It is the only subcutaneous CD38-directed antibody approved to treat patients with multiple myeloma. DARZALEX FASPRO is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.

INDICATIONS

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:

In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor
In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent
For more information, visit www.DARZALEX.com.

DARZALEX FASPRO IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

DARZALEX FASPRO is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation.

WARNINGS AND PRECAUTIONS

Hypersensitivity and Other Administration Reactions

Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO.

Systemic Reactions

In a pooled safety population of 898 patients with multiple myeloma (N=705) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO as monotherapy or in combination, 9% of patients experienced a systemic administration-related reaction (Grade 2: 3.2%, Grade 3: 1%). Systemic administration-related reactions occurred in 8% of patients with the first injection, 0.3% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 3.2 hours (range: 4 minutes to 3.5 days). Of the 140 systemic administration-related reactions that occurred in 77 patients, 121 (86%) occurred on the day of DARZALEX FASPRO administration. Delayed systemic administration-related reactions have occurred in 1% of the patients.

Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.

Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.

Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO.

Local Reactions

In this pooled safety population, injection-site reactions occurred in 8% of patients, including Grade 2 reactions in 0.7%. The most frequent (>1%) injection-site reaction was injection-site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO. Monitor for local reactions and consider symptomatic management.

Neutropenia

Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO, higher rates of Grade 3-4 neutropenia were observed.

Thrombocytopenia

Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Consider withholding DARZALEX FASPRO until recovery of platelets.

Embryo-Fetal Toxicity

Based on the mechanism of action, DARZALEX FASPRO can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO and for 3 months after the last dose.

The combination of DARZALEX FASPRO with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy.

Interference With Serological Testing

Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted.

Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO. Type and screen patients prior to starting DARZALEX FASPRO.

Interference With Determination of Complete Response

Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO-treated patients with IgG kappa myeloma protein.

ADVERSE REACTIONS

In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, upper respiratory tract infection, peripheral sensory neuropathy, constipation, pneumonia, and peripheral edema.

The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.

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