On July 27, 2023 Astrazeneca reported that high-level results from the primary analysis of the ongoing DESTINY-PanTumor02 Phase II trial showed Enhertu (trastuzumab deruxtecan) demonstrated clinically meaningful progression-free survival (PFS) and overall survival (OS) in previously treated patients across multiple HER2-expressing advanced solid tumours, two secondary endpoints of the trial (Press release, AstraZeneca, JUL 27, 2023, View Source [SID1234633438]).

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In the primary analysis, Enhertu continued to show durable responses based on investigator-assessed confirmed objective response rate (ORR), the primary endpoint of the trial, and duration of response (DoR), a secondary endpoint; reinforcing results from an interim analysis of the trial recently presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: "The progression-free survival and overall survival results for Enhertu alongside the continued robust and durable tumour responses seen with further follow up underscore the potential value of this important medicine for patients with HER2-expressing cancers who currently have no targeted treatment options. With a high unmet need in these cancers, we are working with health authorities to bring Enhertu to patients with HER2-expressing cancers that could potentially benefit from this medicine as quickly as possible."

Mark Rutstein, Global Head, Oncology Development, Daiichi Sankyo, said: "These updated results from the DESTINY-PanTumor02 trial are important as we work to reshape the clinical landscape in HER2-expressing advanced cancers, where patients currently have limited treatment options and face a poor prognosis. The overall survival demonstrated by Enhertu in these patients is a significant step forward in the potential to advance current standards of care and offer new options for patients with HER2-expressing cancers."

The DESTINY-PanTumor02 Phase II trial is evaluating the efficacy and safety of Enhertu in patients with previously treated locally advanced, unresectable, or metastatic HER2-expressing solid tumours not eligible for curative therapy, including biliary tract, bladder, cervical, endometrial, ovarian, pancreatic, and other cancers.

The safety profile observed in the primary analysis was consistent with prior data and with other trials of Enhertu with no new safety concerns identified. Interstitial lung disease (ILD) rates and severity were consistent with those observed in other trials of Enhertu, with a low rate of Grade 5 ILD events observed as determined by an independent adjudication committee.

These data will be presented at a forthcoming medical meeting and will support ongoing discussions with global health authorities.

Notes

HER2 expression in solid tumours
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of various tissue cells throughout the body and is involved in normal cell growth.1,2 In some cancers, HER2 expression is amplified or the cells have activating mutations.1,3 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis.4

While HER2-directed therapies have been used to treat breast, gastric, lung and colorectal cancers, more research is needed evaluating their potential role in treating other HER2-expressing tumour types.2,5,6

HER2 is an emerging biomarker in biliary tract, bladder, cervical, endometrial, ovarian and pancreatic cancers.3 Testing is not routinely performed in these additional tumour types and as a result, available literature is limited. HER2 overexpression (IHC3+) has been observed at rates from 1% to 28% in these solid tumours.7,8 There is an unmet need for effective therapies for certain HER2-expressing solid tumours, particularly for those who have progressed on or are refractory to standard of care therapies as there are currently no approved HER2-directed therapies for these cancers.2,9

DESTINY-PanTumor02
DESTINY-PanTumor02 is a global, multicentre, multi-cohort, open-label Phase II trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) for the treatment of previously treated HER2-expressing tumours, including biliary tract cancer, bladder cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer and other tumours.

The primary efficacy endpoint of DESTINY-PanTumor02 is confirmed ORR as assessed by investigator. Secondary endpoints include DoR, disease control rate, PFS, OS, safety, tolerability and pharmacokinetics.

DESTINY-PanTumor02 has enrolled 267 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Enhertu (5.4mg/kg) is approved in more than 50 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

Enhertu (5.4mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in-situ hybridisation [ISH]-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

Enhertu (5.4mg/kg) is approved in Israel and under accelerated approval in the US for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval for this indication in the US may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial and/or DESTINY-Gastric02 trial.

Enhertu development programme
A comprehensive global development programme is underway evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

On July 27, 2023 Checkpoint Therapeutics, Inc. ("Checkpoint") (Nasdaq: CKPT), a clinical-stage immunotherapy and targeted oncology company, reported new, longer-term data for cosibelimab from its pivotal studies in locally advanced and metastatic cutaneous squamous cell carcinoma ("cSCC") (Press release, Checkpoint Therapeutics, JUL 27, 2023, View Source [SID1234633437]). These results demonstrate a deepening of response over time, resulting in substantially higher complete response rates than previously reported. Furthermore, responses continue to remain durable over time with the median duration of response not yet reached in either group. Results determined by independent central review by treatment group were as follows:

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Parametera Locally Advanced cSCC
(n=31) Metastatic cSCC
(n=78)
Data cutoff Mar 2022 Jan 2023 Nov 2021 Jan 2023
Objective response rate
(95% confidence interval) 55%
(36%, 73%) 55%
(36%, 73%) 47%
(36%, 59%) 50%
(39%, 62%)
Complete response rate 10 % 23 % 8 % 13 %
Partial response rate 45 % 32 % 39 % 37 %
Response ongoing 82 % 82 % 73 % 69 %
Median duration of response Not reached Not reached Not reached Not reached
a As assessed by independent central review.

"We are excited to see the substantial increases in the rate of patients experiencing a complete response of their cSCC tumors with further cosibelimab treatment in both our locally advanced and metastatic pivotal trials," said James Oliviero, President and Chief Executive Officer of Checkpoint. "We believe cosibelimab’s strong efficacy and response durability are driven by its unique two-fold mechanism of action in which cosibelimab binds to PD-L1 with sustained high target tumor occupancy to reactivate the body’s T-cell anti-tumor response, with the addition of a functional Fc domain to activate the body’s natural killer immune cells to induce antibody-dependent cell-mediated cytotoxicity of tumor cells, resulting in a powerful one-two punch to eradicate tumors. We expect this dual mechanism of action to benefit not just immunocompetent patients, but also the large number of difficult-to-treat patients with immunosuppressive conditions or taking immunosuppressive medications who continue to suffer poor outcomes with currently available treatments."

Updated safety data across 247 patients enrolled and treated with cosibelimab in all cohorts of the ongoing study remain consistent with those previously reported, with only 2% of patients experiencing a severe immune-related adverse event ("irAE") and less than 1% of patients discontinuing treatment due to an irAE of any severity, both substantially lower than the rates observed with currently approved immunotherapies.

Mr. Oliviero continued, "Unlike PD-1 inhibitors, cosibelimab does not interrupt the body’s PD-1/PD-L2 pathway, which we believe results in cosibelimab’s low rates of autoimmunity. We believe cosibelimab’s favorable safety profile should position the product as the preferred immunotherapy of oncologists for the large number of high-risk cSCC patients, such as those with solid organ transplants or autoimmune disease, upon its potential launch early next year. If our Biologics License Application ("BLA") is approved in the coming months, based on its unique mechanism of action and compelling efficacy and safety profile, we believe cosibelimab, as a differentiated and possibly best-in-class treatment, has the potential to become the market leading immunotherapy for patients with cSCC, which we estimate to be a $1.6 billion annual U.S. market opportunity."

In January 2023, Checkpoint submitted a BLA to the U.S. Food and Drug Administration ("FDA") seeking approval of cosibelimab as a treatment for patients with metastatic cSCC or locally advanced cSCC who are not candidates for curative surgery or radiation. The application is filed and under review with a Prescription Drug User Fee Act ("PDUFA") goal date of January 3, 2024.

Checkpoint plans to present these updated results at an upcoming medical conference.

On July 26, 2023 GlaxoSmithKline reported its second quarter 2023 results (Press release, GlaxoSmithKline, JUL 26, 2023, View Source [SID1234634669]).

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On July 26, 2023 The University of Texas MD Anderson Cancer Center and Nexo Therapeutics reported a multi-year strategic collaboration that aligns the innovative technology and capabilities of each organization at the earliest stages of drug discovery and development to rapidly advance impactful new cancer therapies against previously undruggable targets (Press release, Nexo Therapeutics, JUL 26, 2023, View Source [SID1234633476]).

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The agreement brings together Nexo’s unique drug discovery platform, which combines innovative covalent chemistry and chemical biology, with the translational research and drug development expertise of MD Anderson’s Translational Research to AdvanCe Therapeutics and Innovation in ONcology (TRACTION) platform. MD Anderson and Nexo will work together from discovery through investigational new drug-enabling studies to accelerate development of small-molecule therapies for patients with limited treatment options.

"We are excited to work with the team of researchers at MD Anderson to discover and develop novel cancer medicines targeting some of the fundamental drivers of cancer that have eluded past efforts," said Andrew Phillips, Ph.D., founder and chief executive officer of Nexo Therapeutics. "By joining our complementary skills and capabilities at the earliest stages of drug discovery, we aim to enhance the prospects of rapidly advancing novel therapies to the clinic."

Many promising cancer targets present significant hurdles for conventional drug development approaches based on the structure of the target as well as selectivity and pharmacological properties of the drug. The Nexo platform aims to systematically address each of these issues by combining a chemistry engine with chemical biology capabilities.

Nexo’s chemistry engine, CODON (Covalent Discovery and Optimization), combines a proprietary library that leverages chemical diversity and innovative covalent chemistries with scalable biochemical and in-cell proteomics. This allows the company to identify promising hit compounds and to conduct rapid optimization to produce compounds for in vivo studies.

The company’s unique chemical biology approach, INFINI-T (Informed Profile Before Initiation of Target), uses the power of chimeric fusion proteins to address target biology and pharmacology questions. The function of these chimeric proteins can be controlled by small molecules in cellular and in vivo models to generate detailed information about the required depth, duration and selectivity of target inhibition. Importantly, the INFINI-T platform provides target product profiles for medicinal chemistry well in advance of lead optimization. This is expected to decrease the time and capital needed to bring drug candidates to the clinic.

"Together with Nexo’s innovative platform, our integrated approach to translational research and drug development is poised to design and rapidly advance novel therapies against high priority oncology targets," said Tim Heffernan, Ph.D., vice president of Oncology Research for TRACTION at MD Anderson. "This collaboration highlights our commitment to advancing innovative new medicines that address critical unmet needs for our patients."

MD Anderson established the TRACTION platform to overcome traditional hurdles in oncology drug development and to quickly and safely advance the right treatments for the right patients. The platform incorporates a variety of cutting-edge technologies, disease modeling approaches and data analytics tools to better inform drug development, from discovery into clinical trials. The TRACTION platform is a core component of MD Anderson’s Therapeutics Discovery division, an integrated team of clinicians, researchers and drug development experts working to advance impactful therapies for cancer.

Beginning at the first stages of drug discovery and target identification, TRACTION researchers will collaborate with Nexo to characterize susceptible cancers, to identify potential combination treatment strategies and to evaluate biomarkers that can optimize patient selection.

Nexo and MD Anderson will collaborate on discovery and translation efforts, with the option to extend the collaboration into clinical development. Nexo will provide research support funding, and MD Anderson is eligible to receive certain royalties and payments based on a range of future development, regulatory, commercial and business milestones. Nexo will retain all rights to programs under the collaboration and will have sole responsibility for development, manufacturing and commercialization.

On July 26, 2023 Integra LifeSciences Holdings Corporation (NASDAQ: IART), a leading global medical technology company, reported its financial results for the second quarter ending June 30, 2023 (Press release, Integra LifeSciences, JUL 26, 2023, View Source [SID1234633456]).

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Second Quarter 2023 Highlights
•Second quarter revenues of $381.3 million declined 4.2% on a reported basis and declined 2.7% on an organic basis compared to the prior year.

•Second quarter GAAP earnings per diluted share of $0.05, compared to $0.54 in the prior year; adjusted earnings per diluted share of $0.71, compared to $0.82 in the prior year
.
•Appointed Lea Daniels Knight as executive vice president and CFO

Share repurchase and 2023 guidance

•Planning a $125 million share repurchase in the third quarter

•Updating full-year 2023 revenue and adjusted earnings per share guidance with a range of $1.548 billion to $1.560 billion and $3.10 to $3.18 respectively, reflecting the impact of the Boston recall and the solid performance of the underlying business

"The strong organic growth of our Codman Specialty Surgical segment and several product lines in our Tissue Technologies business demonstrate the resilience of our diversified portfolio of leading brands and technologies and strong market recovery. Excluding the impact of the Boston recall, we delivered solid, mid-single digit organic growth from the underlying business," said Jan De Witte, Integra LifeSciences’ president and chief executive officer. "We are confident in our plans for the CereLink relaunch and the restart of our Boston manufacturing facility, and we continue to advance our implant-based breast reconstruction (IBBR) PMA strategy."

Second Quarter 2023 Consolidated Performance

Total reported revenues of $381.3 million declined 4.2% on a reported basis and declined 2.7% on an organic basis compared to the prior year.
The Company reported GAAP gross margin of 54.3%, compared to 62.7% in the second quarter of 2022. Adjusted gross margin was 67.6%, compared to 68.0% in the prior year.
Adjusted EBITDA for the second quarter of 2023 was $88.8 million, or 23.3% of revenue, compared to $102.8 million, or 25.8% of revenue, in the prior year.
The Company reported GAAP net income of $4.2 million, or $0.05 per diluted share, in the second quarter of 2023, compared to a GAAP net income of $44.8 million, or $0.54 per diluted share, in the prior year.
Adjusted net income for the second quarter of 2023 was $57.4 million, or $0.71 per diluted share, compared to $68.3 million, or $0.82 per diluted share, in the prior year.

Second Quarter 2023 Segment Performance
Codman Specialty Surgical (~71% of Revenues)
•Total revenues were $271.0 million, representing reported growth of 5.1% and organic growth of 6.3% compared to the second quarter of 2022, due to high single-digit growth in Advanced Energy driven by CUSA capital and disposables; mid-single-digit growth in CSF management driven by Certas Plus valves and BactiSeal; mid-single-digit growth in Dural Access and Repair driven by Mayfield and DuraGen; low single-digit decline in Neuro Monitoring driven by CereLink and low double-digit growth in Instruments.

Tissue Technologies (~29% of Revenues)

•Total revenues were $110.2 million, representing reported decline of 21.2% and organic decline of 19.7% compared to the second quarter of 2022, due to the impact of the lost revenue and return provision for the Boston recall which was partially offset by double digit growth from MicroMatrix, Cytal, MediHoney and nerve franchise.
Key Products and Business Highlights

•Positive global demand performance across the portfolio
•Expect to restart manufacturing at the Boston facility late Q4’23 and resume commercial distribution in mid- to late Q2’24
•Relaunch of CereLink expected late Q3’23 in international markets and late Q4’23 in the US
•Advancing IBBR PMA strategy
◦Submitted clinical PMA amendment for SurgiMend
◦Completed enrollment In DuraSorb Monofilament Mesh U.S. investigational device exemption study
•Expanded global DuraGen portfolio with approvals in China and Japan
•Launched CUSA Lap Tip in Japan, Canada, South Africa and Israel
•Positive clinical and economic outcomes for Codman Bactiseal EVD Catheter from real-world evidence study in Europe
•Opened Dr. Richard E. Caruso Center of Innovation and Learning in Plainsboro, New Jersey

Balance Sheet, Cash Flow and Capital Allocation
The Company generated cash flow from operations of $28.3 million in the quarter. Total balance sheet debt and net debt at the end of the quarter were $1.44 billion and $1.13 billion, respectively, and the consolidated total leverage ratio was 2.6x.

As of quarter end, the Company had total liquidity of approximately $1.61 billion, including $309.2 million in cash and the remainder available under the revolving credit facility.

Share Repurchase Program

The Company is planning for a $125 million share repurchase during the third quarter under an authorization of the Company’s board of directors.

2023 Outlook
For the full year 2023, the Company is updating its revenue and adjusted EPS expectations to $1.548 to $1.560 billion and $3.10 to $3.18, respectively. The revenue range represents reported growth of -0.6% to 0.2%, with organic growth of 0.3% to 1.1% and reflects the full year impact of the Boston recall and the solid performance of the underlying business.

For the third quarter 2023, the Company expects reported revenues in the range of $386 million to $390 million, representing reported growth of 0.2% to 1.3% and organic growth of 0.3% to 1.3%. Adjusted earnings per diluted share are expected to be in the range of $0.76 to $0.80, including the impact of the Boston recall.

The Company’s guidance for the third quarter and full-year organic sales growth excludes acquisitions and divestitures, the effects of foreign currency and the year-over-year change in revenue from discontinued products. Organic growth excludes sales from the divestiture of the Company’s traditional wound care (TWC) business as of September 1, 2022, and sales from the acquisition of Surgical Innovation Associates, Inc. (SIA) through December 1, 2023. Adjusted earnings per share guidance reflects the impact of the divestiture of the TWC business, the SIA acquisition and the impact of foreign currency.

Conference Call and Presentation Available Online
Integra has scheduled a conference call for 8:30 a.m. ET on Thursday, July 27, 2023, to discuss second quarter 2023 financial results and forward-looking financial guidance. The conference call will be hosted by Integra’s senior management team and will be open to all listeners. Additional forward-looking information may be discussed in a question-and-answer session following the call. Integra’s management team will reference a presentation during the conference call, which can be found on the Investor section of the website at investor.integralife.com.

A live webcast will be available on the Investors section of the Company’s website at investor.integralife.com. For those planning to participate on the call, register here to receive dial-in details and an individual pin. While not required, it is recommended to join 10 minutes prior to the event’s start. A webcast replay of the conference call will be available on the Investors section of the Company’s website following the call.