On March 29, 2023 IceCure Medical Ltd. (Nasdaq: ICCM) (TASE: ICCM) developer of the ProSense System of minimally-invasive cryoablation technology that destroys tumors by freezing, reported audited financial results as of and for the twelve months ended December 31, 2022 (Press release, IceCure Medical, MAR 29, 2023, View Source;recent-corporate-developments-milestone-achievements-expected-to-drive-revenue-growth-in-2023-301784497.html [SID1234629518]).

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"Our success throughout 2022 and the trends we are currently experiencing position us to make significant commercial advances in key markets, including in the U.S., for the ProSense platform for early-stage breast cancer and in China where our cryoprobes recently received approval for commercial use in combination with our cryoablation system console, which was previously approved. Commercialization in China is driven by our exclusive distribution agreement with Shanghai Medtronic Zhikang Medical Devices Co. Ltd., an affiliate of Medtronic ("Shanghai Medtronic Zhikang"), the world’s largest medical device company, which includes minimum purchase targets," stated Eyal Shamir, IceCure’s Chief Executive Officer. "We believe that our achievements in 2022, which included regulatory, reimbursement, clinical, and commercial milestones, provide us with a solid foundation to execute our growth strategy to drive revenues in the years to come.

"Our rising confidence is bolstered by accelerated sales of our disposable cryoprobes in the U.S., demonstrating that the previously installed ProSense systems are increasingly being utilized by physicians. We also believe our strengthened balance sheet, which includes the $14.5 million we raised in December 2022, allows us to expand our global marketing footprint. The capital resources we have will enable us to execute on our commercialization plans throughout 2023 and beyond while ensuring we can also invest in future generations of our novel technology."

Significant Operating, Clinical, Regulatory & Commercial Highlights

Rising Awareness and Utilization of ProSense System: System and disposables sales in the U.S. represented 20% of 2022 revenues, up from 11% in 2021, as increased utilization of systems generated a 28% year-over-year increase in U.S. sales. Worldwide, disposable sales accounted for 43% of 2022 revenue, up from 29% in 2021.
Filed for FDA Marketing Authorization of ProSense for Breast Cancer: The Company submitted a De Novo Classification Request regulatory filing with the U.S. Food and Drug Administration ("FDA") for marketing authorization based on ICE3 clinical trial ("ICE3") interim analysis for the indication of early-stage (Luminal A T1 invasive) low-risk breast cancer in patients who are at high risk to surgery (not suitable for surgical alternatives). This indication alone represents approximately 43,000 women in the U.S. annually.
Initial Medicare Reimbursement Code for ProSense Established: The Centers for Medicare & Medicaid Services ("CMS") assigned ProSense breast cancer cryoablation procedures with a CPT Category III reimbursement code setting the facility fee at $3,400 per procedure. Additional reimbursement coverage, including payment for the physician, is expected upon CMS establishing the permanent CPT Category I code, which is conditioned on several factors, particularly the Company’s receipt of FDA marketing authorization of ProSense for breast cancer.
Received Regulatory Approval in China for Commercial Use of Cryoprobes in 2023: The National Medical Products Administration ("NMPA") of China approved the IceSense3 (ProSense’s brand name in China) disposable cryoprobes for commercial use, to be used in combination with the Company’s IceSense3 system console, which was previously approved by the NMPA.
Signed China Distribution Agreement with Shanghai Medtronic Zhikang Medical Devices Co. Ltd.: IceCure’s wholly-owned subsidiary, IceCure (Shanghai) MedTech Co., Ltd. ("IceCure Shanghai"), signed an exclusive distribution agreement for IceSense3 cryoablation systems with Shanghai Medtronic Zhikang and Beijing Turing Medical Technology Co. Ltd. ("Turing"), to be the exclusive distributors of the IceSense3 and its disposable probes in mainland China for an initial period of three years, with minimum purchase targets of $3.5 million for this period.
Patents Granted in U.S. and Japan: IceCure received patents in the U.S. and Japan for its novel cryogenic pump, potentially broadening the clinical indications addressed by the Company’s platform technology.
Achieved Regulatory Milestones in Major Global Markets—Additional Responses Expected in 2023: ProSense cryoprobes and introducers received regulatory approval in Brazil for several indications, including breast and other cancers, benign tumors, and palliative intervention. Approval for the ProSense system is currently pending in Brazil, and a response from the Brazilian Health Regulatory Agency ("ANVISA") is expected in 2023. Applications for regulatory approval of ProSense and its accessories were filed in Canada and Vietnam.
Presented Interim Study Results Showing ProSense is Safe and Effective in Treating Kidney Tumors with 89.5% Recurrence-Free Rate: At the Urological Association Conference in Israel, the Company presented interim findings from its ICESECRET study for the treatment of patients with small renal masses ("SRM") who cannot be offered kidney-preserving surgery. ProSense was found to be a safe and effective treatment method for renal lesions smaller than 5 cm in patients not suitable for kidney-preserving surgery. In a subgroup of patients with no previous history of kidney cancer on the same kidney and a lesion ≤3 cm, an 89.5% recurrence-free rate was observed at a mean follow-up time of 22.2 months when the procedure protocol was followed. ProSense is approved for the treatment of benign and malignant kidney tumors in the U.S., Europe, and numerous other countries.
Strengthened Balance Sheet

As of December 31, 2022, the Company had cash and cash equivalents including short-term deposits of approximately $23.7 million, compared to approximately $25.6 million as of December 31, 2021. The Company will use its resources to execute its global business strategy and continue to raise awareness of the clinical and economic benefits of its ProSense system.

Financial Results for the Twelve Months Ended December 31, 2022

For the twelve months ended December 31, 2022, the Company reported revenue of $3.1 million compared to revenue of $4.1 million for the twelve months ended December 31, 2021. As previously disclosed on February 9, 2023, the year-over-year decline was due to lower revenue recognition of approximately $0.6 million from the distribution agreements with Terumo Corporation and a decrease in sales of new systems, mostly in Thailand. This was partially offset by higher revenue from sales of the Company’s disposable probes, as previously sold and installed systems were utilized for procedures in clinical settings, as well as higher sales in the U.S. compared to the prior year period.

Gross profit was approximately $1.4 million for the twelve months ended December 31, 2022, compared to approximately $2.1 million for the twelve months ended December 31, 2021. Gross margin was approximately 47% for the twelve months ended December 31, 2022, compared to approximately 53% for the twelve months ended December 31, 2021. The decrease in gross margin compared to the same period last year was attributable to the decrease in revenue recognition from the Terumo distribution agreements.

Research and development expenses for the twelve months ended December 31, 2022, were approximately $9.1 million compared to approximately $5.9 million for the twelve months ended December 31, 2021. The increase was primarily due to the development of IceCure’s next-generation single-probe system, along with increased clinical and regulatory activities, including the FDA and NMPA submissions.

Sales and marketing expenses for the twelve months ended December 31, 2022 were approximately $3.2 million, compared to approximately $1.9 million for the twelve months ended December 31, 2021. The increase was attributed to the Company’s expanding commercialization efforts in the U.S. and other territories.

General and administrative expenses for the twelve months ended December 31, 2022 were approximately $5.9 million, compared to approximately $4.1 million for the twelve months ended December 31, 2021. The increase was attributed to the Company’s increased Nasdaq listing-related expenses.

Total operating expenses for the twelve months ended December 31, 2022 were approximately $18.2 million, compared to approximately $11.9 million for the twelve months ended December 31, 2021. The increase in operating expenses was primarily attributable to increased development, commercialization, and Nasdaq listing-related activities. As a result of lower revenue and increased operating activities, net loss reported for the twelve months ended December 31, 2022 increased to approximately $17.0 million, or $0.46 per share, compared with a net loss of approximately $9.9 million, or $0.35 per share, for the same period last year.

Conference call information:

The Company will discuss its results today via teleconference at 10:00 a.m. Eastern Time. To access the live call, dial 1-888-642-5032 (U.S. toll-free) or +972-3-9180609 (International) and ask to join the IceCure earnings call. An archived recording of the call will also be accessible on the "Investors" section of our website at www.icecure-medical.com.

On March 29, 2023 FACIT reported $1.5 billion in follow-on investment attracted to its portfolio of cancer biotechnology start-ups in Ontario, a significant milestone for life science commercialization in Canada (Press release, FACIT, MAR 29, 2023, View Source [SID1234629517]). FACIT partners with start-ups to commercialize their made-in-Ontario technologies and intellectual property (IP). With FACIT’s expertise and seed capital, Ontario companies have gone on to create skilled jobs and high-tech facilities while keeping homegrown talent from leaving the province.

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"This financing milestone represents a major win for Ontario’s innovation economy, and an unprecedented return on research investment for taxpayers," said Dr. David O’Neill, President of FACIT. "It also signals hope for the two-in-five Ontarians who will be diagnosed with cancer and could have their cancer prevented, detected or treated by one of these innovations."

FACIT and its strategic research partner, the Ontario Institute for Cancer Research (OICR), were created to capitalize on Ontario’s world-renowned medical research hub. To achieve this bold commercialization strategy, FACIT created its Prospects Oncology and Compass Rose Oncology Funds to invest in Ontario entrepreneurs and seed a domestic industrial pathway to drive cancer clinical trials and economic development.

By leveraging early investment exits, FACIT has established its own source of risk-capital and demonstrated the value of capitalizing on Ontario life sciences IP. Following consecutive waves of commercialization success, FACIT has made approximately $60 million in private sector returns available for reinvestment into Ontario innovation and the next generation of biotech leaders, including CTRL Therapeutics, Fusion Pharmaceuticals, Radiant Biotherapeutics, Tenomix, Xpan and others.

Given the global health marketplace is worth $10 trillion, capturing even a 1% share from homegrown IP could be a major boon for the economy, for cancer research, and for the patients who benefit from new breakthroughs.

"Implementing the principles of seed venture investing in a public research setting establishes an Ontario First pathway for cancer innovation," Dr. O’Neill added. "With over 30 times leverage from the private sector, this novel commercialization venture has created tremendous value from homegrown IP, advancing start-ups and accelerating clinical trials."

"Congratulations to FACIT on the impressive growth of its portfolio companies and the success of its groundbreaking approach to commercialization. OICR’s unique partnership with FACIT continues to generate great outcomes in our joint mission to advance cancer research innovations led by OICR researchers and their key collaborators to improve outcomes for people with cancer and grow Ontario’s economy," said Dr. Laszlo Radvanyi, President and Scientific Director of OICR.

"Our government is focused on the long-term economic growth of Ontario by supporting entrepreneurs and making key investments in research and innovation," said Jill Dunlop, Minister of Colleges and Universities. "Ontario’s support for leading organizations like FACIT highlights our province’s commitment to maximizing the value of made-in-Ontario research and intellectual property, so we can increase commercialization opportunities and ultimately help our discoveries reach patients so they can lead longer and healthier lives."

"Through our Life Sciences Strategy, we’re ensuring Ontario remains at the forefront of innovation and continues to be a global leader in life sciences," said Vic Fedeli, Minister of Economic Development, Job Creation and Trade. "FACIT’s milestone is great news for the sector and an important step forward in Ontario cancer innovation. We’re committed to adopting innovative approaches to secure and grow our position as an attractive destination to do business."

About FACIT

On March 29, 2023 Coeptis Therapeutics Holdings, Inc. (NASDAQ: COEP) ("Coeptis" or "the Company"), a biopharmaceutical company developing innovative cell therapy platforms for cancer, reported it has obtained the exclusive right to negotiate towards the acquisition of VyGen-Bio, Inc. or its assets (Press release, Coeptis Therapeutics, MAR 29, 2023, https://www.prnewswire.com/news-releases/coeptis-therapeutics-secures-exclusive-rights-to-negotiate-to-acquire-transformational-cell-therapy-platform-to-enable-potent-combinatorial-immuno-oncology-treatment-strategies-301784036.html [SID1234629516]). Coeptis intends to immediately commence its due diligence review of VyGen-Bio’s assets, including its IP and knowhow related to rights to GEAR cell therapy and companion diagnostic platforms, and, depending on the results of its due diligence analysis, turn to negotiation of definitive deal documents. VyGen-Bio’s product candidates and platforms were discovered by scientists at the world-renowned Karolinska Institutet in Stockholm, Sweden, including Dr. Arnika Wagner, who is expected to play a key collaborative development role for Coeptis as the Company builds its capabilities to develop treatments for cancer and gains technologies to develop additional cell and gene therapies.

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This transaction, if finalized, would expand upon Coeptis’ collaboration with VyGen-Bio, which is currently focused on CD38-GEAR-NK, a natural killer (NK) cell therapy for the treatment of CD38+ cancers with an initial focus on multiple myeloma, and CD38-Diagnostic, an in vitro diagnostic tool being developed to help identify cancer patients who may be appropriate candidates for anti-CD38 mAb therapy.

In the event a transaction is consummated, Coeptis would then be in a position to advance the development of various GEAR-engineered cells, including NK cells, T cells, and hematopoietic stem cells, and to pursue development of GEAR-engineered cells for use in combination with mAbs that target a potentially wide range of receptor targets. Additional development options that would be explored could include therapeutic modalities where the antigen-specificity of mAbs is used, such as CAR-T and bispecific antibodies for the treatment of a broad range of hematologic malignancies and solid tumors.

"We believe that the acquisition of VyGen-Bio’s GEAR Platform would represent a significant inflection point in the growth of Coeptis and our strategy to be a leader in the development of ‘next generation’ cell therapy technologies for cancer and other diseases," said Dave Mehalick, President and CEO of Coeptis Therapeutics. "Our vision for GEAR is bold and ambitious, as we believe this novel cell engineering approach protects the integrity, fitness and function of the cell while importantly shielding it from destruction by co-administered mAbs. We believe the GEAR platform offers the potential to not only improve existing cancer therapies, but further expand the use of existing therapies in new indications."

"If we are able to successfully consummate an acquisition transaction, we plan to initially focus on advancing the first GEAR candidate, CD38-GEAR-NK, to the clinic for the treatment of multiple myeloma and to concurrently engage in business development activities to expand the GEAR Platform into new cell therapy products via potential co-development and/or licensing partnerships," Mehalick added.

GEAR was discovered by scientists at the Karolinska Institutet (KI), including Evren Alici M.D., Ph.D., Hans-Gustaf Ljunggren M.D., Ph.D., and Arnika Kathleen Wagner Ph.D. Drs. Alici, Ljunggren, and Wagner are founding members of VyGen-Bio and will continue to contribute in the development of the technology platforms as members of Coeptis’ Scientific Advisory Board. Drs. Ljunggren and Alici are managing directors of NextGenNK, an international Competence Center for the development of next-generation NK cell-based cancer immunotherapies based at KI and funded by Sweden’s innovations agency, Vinnova. KI is globally recognized for its Nobel Assembly, which awards the Nobel Prize in Physiology or Medicine.

"GEAR-NK cells, and ultimately all GEAR-engineered cells, are being designed to potentially decrease side-effects associated with certain mAb therapies and potentially reduce or eliminate the ‘on-target-off-tumor’ effect. As a Coeptis’ SAB member, I look forward to collaborating in the development of these technologies, which may have widespread applicability in cancer and beyond," stated GEAR co-inventor, Dr. Wagner.

On March 29, 2023 The Janssen Pharmaceutical Companies of Johnson & Johnson reported new long-term data from the CHRYSALIS study evaluating RYBREVANT (amivantamab-vmjw) in patients with advanced non-small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease progressed on prior platinum-based chemotherapy (Press release, Janssen Pharmaceuticals, MAR 29, 2023, View Source [SID1234629515]). Data from the study showed long-term response and safety in this population and were presented in an oral presentation at the 2023 European Lung Cancer Congress (ELCC) (Abstract #779).1

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In the analysis of the CHRYSALIS study, investigators assessed the efficacy and safety of RYBREVANT in patients (n=114) with NSCLC and EGFR exon 20 insertion mutations, who had progressed on prior platinum-based chemotherapy, and were treated at the approved Phase 2 dose of 1050 mg (1400 mg for a patient weight of at least 80 kg).1 The primary endpoint was overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1* (RECIST v1.1).1 Additional endpoints included duration of response (DOR), clinical benefit rate, progression-free survival (PFS) and overall survival (OS).1

After a median follow-up of 19.2 months, the median OS with RYBREVANT treatment was 23 months (95 percent Confidence Interval [CI], 18.5–29.5) with a two-year OS rate of 47 percent.1 The investigator-assessed ORR was 37 percent (95 percent CI, 28–46) with a median DOR of 12.5 months (95 percent CI, 6.9–19.3), and median PFS of 6.9 months (95 percent CI, 5.6-8.8).1 Across subgroups, treatment with RYBREVANT resulted in consistent efficacy across post-platinum patients with EGFR exon 20 insertion mutations, including the elderly, regardless of prior therapies or response to prior platinum chemotherapy.1 Forty-eight patients (42 percent) had sustained clinical response measured by ORR on RYBREVANT for at least 12 cycles.1 The median duration of treatment was 7.5 months and treatment is ongoing in 15 patients (13 percent) who have received RYBREVANT for a median of 2.6 years.1 Of these patients, seven are progression-free and eight are receiving treatment beyond progression.1

No new safety signals were identified and rash (all group, 89 percent), infusion-related reactions (IRR; 67 percent) and paronychia (58 percent) remained the most common treatment emergent adverse events (AEs).1 The incidence of treatment-related AEs leading to dose interruption, reduction and discontinuation was 29 percent, 18 percent and seven percent, respectively.1

"With these new data, amivantamab showed long-term consistent efficacy regardless of prior therapies or response to prior platinum chemotherapy," said Pilar Garrido♦, M.D., Associate Professor of Medical Oncology at Universidad de Alcalá, Head of Medical Oncology Department at the University Hospital Ramón y Cajal in Madrid, Spain and principal investigator. "Due to the aggressive nature of NSCLC with EGFR exon 20 insertion mutations, treatment with targeted therapies is an important consideration when identifying a treatment option for patients."

NSCLC driven by EGFR exon 20 insertion mutations carries a worse prognosis and shorter survival rates compared with lung cancer driven by more common EGFR mutations, such as exon 19 deletions and L858R substitutions.2 The standard of care for common EGFR mutations, such as EGFR tyrosine kinase inhibitor (TKIs), are generally inactive against exon 20 insertion mutations and are not FDA-approved for these patients.2

"The long-term CHRYSALIS data presented at ELCC support RYBREVANT as an important treatment option for patients with EGFR exon 20 insertion mutation-positive NSCLC, providing valuable clinical insights that may help inform treatment decisions," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Janssen Research & Development, LLC. "We’re committed to transforming the treatment of lung cancer through continued research and the development of targeted therapies for gene-mutated disease where high unmet needs continue to exist."

About the CHRYSALIS Study
CHRYSALIS (NCT02609776) is a Phase 1 open-label, multicenter, first-in-human study to evaluate the safety, pharmacokinetics and preliminary efficacy of RYBREVANT as a monotherapy and in combinations including with lazertinib*, a novel third-generation EGFR TKI3, in adults with advanced NSCLC.4 The study consists of two parts: RYBREVANT monotherapy and combination-dose escalations (Part 1) and RYBREVANT monotherapy and combination-dose expansions (Part 2). The study enrolled 780 patients with advanced NSCLC.5

In the ongoing CHRYSALIS study, patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations weighing less than 80 kg received RYBREVANT 1050 mg and patients weighing at least 80 kg or more received RYBREVANT 1400 mg weekly for four weeks, with the initial dose as a split infusion in week 1 on day 1 and day 2, then administered every two weeks thereafter until disease progression or unacceptable toxicity.5 Disease response using ORR, per Response Evaluation Criteria in Solid Tumors Version 1.1** (RECIST v1.1) as evaluated by Blinded Independent Central Review (BICR), was the primary endpoint.

About RYBREVANT
RYBREVANT (amivantamab-vmjw) received accelerated approval by the U.S. Food and Drug Administration (FDA) in May 2021 for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.6 This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. RYBREVANT has also received approval from health authorities in Europe, as well as other markets around the world.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer◊ prefer NGS-based strategies over PCR-based approaches for the detection of EGFR exon 20 insertion variants and include amivantamab-vmjw (RYBREVANT) as a subsequent therapy option with a Category 2A recommendation for patients that have progressed on or after platinum-based chemotherapy with or without immunotherapy and have EGFR exon 20 insertion mutation-positive advanced NSCLC.7†^

RYBREVANT is being studied in multiple clinical trials in NSCLC, including:

As first-line therapy in the Phase 3 MARIPOSA (NCT04487080) study assessing amivantamab in combination with lazertinib, a novel third generation EGFR TKI, against osimertinib and against lazertinib alone in untreated advanced EGFR-mutated NSCLC.8
The Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of lazertinib, amivantamab and carboplatin-pemetrexed versus carboplatin-pemetrexed in patients with locally advanced or metastatic EGFR exon 19 deletion or exon 21 L858R substitution NSCLC after osimertinib failure.9
The Phase 1/1b CHRYSALIS-2 (NCT04077463) study evaluating amivantamab in combination with lazertinib and lazertinib as a monotherapy in patients with advanced NSCLC with EGFR mutations.10
The Phase 3 PAPILLON (NCT04538664) study assessing amivantamab in combination with carboplatin-pemetrexed versus chemotherapy alone in patients with advanced or metastatic EGFR-mutated NSCLC and exon 20 insertion mutations.11
The Phase 1 PALOMA (NCT04606381) study assessing the feasibility of subcutaneous (SC) administration of amivantamab based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for amivantamab SC delivery.12
The Phase 2 PALOMA-2 (NCT05498428) study assessing amivantamab in participants with advanced or metastatic solid tumors including EGFR-mutated NSCLC.13
The Phase 3 PALOMA-3 (NCT05388669) study assessing lazertinib with subcutaneous amivantamab as compared to intravenous amivantamab in participants with EGFR-mutated advanced or metastatic NSCLC.14
The Phase 1/2 METalmark (NCT05488314) study assessing amivantamab and capmatinib combination therapy in unresectable metastatic NSCLC.15
For more information, visit: View Source

About Non-Small Cell Lung Cancer
Worldwide, lung cancer is one of the most common cancers, and NSCLC makes up 80 to 85 percent of all lung cancers.3 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.3 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase supporting cell growth and division.3 EGFR mutations are present in 10 to 15 percent of people with NSCLC adenocarcinoma and occur in 40 to 50 percent of Asians.3 The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent.3 Patients with EGFR exon 20 insertion mutations have a real-world five-year OS of eight percent in the frontline setting, which is worse than patients with EGFR exon 19 deletions or L858R mutations, who have a real-world five-year OS of 19 percent.3

RYBREVANT IMPORTANT SAFETY INFORMATION5

WARNINGS AND PRECAUTIONS  

Infusion Related Reactions
RYBREVANT can cause infusion related reactions (IRR); signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. 

Based on the safety population, IRR occurred in 66% of patients treated with RYBREVANT. Among patients receiving treatment on Week 1 Day 1, 65% experienced an IRR, while the incidence of IRR was 3.4% with the Day 2 infusion, 0.4% with the Week 2 infusion, and cumulatively 1.1% with subsequent infusions. Of the reported IRRs, 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. The median time to onset was 1 hour (range 0.1 to 18 hours) after start of infusion. The incidence of infusion modifications due to IRR was 62% and 1.3% of patients permanently discontinued RYBREVANT due to IRR.   

Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT as recommended. Administer RYBREVANT via a peripheral line on Week 1 and Week 2. Monitor patients for any signs and symptoms of infusion reactions during RYBREVANT infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT based on severity. 

Interstitial Lung Disease/Pneumonitis
RYBREVANT can cause interstitial lung disease (ILD)/pneumonitis. Based on the safety population, ILD/pneumonitis occurred in 3.3% of patients treated with RYBREVANT, with 0.7% of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) discontinued RYBREVANT due to ILD/pneumonitis.  

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold RYBREVANT in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed. 

Dermatologic Adverse Reactions
RYBREVANT can cause rash (including dermatitis acneiform), pruritus and dry skin. Based on the safety population, rash occurred in 74% of patients treated with RYBREVANT, including Grade 3 rash in 3.3% of patients. The median time to onset of rash was 14 days (range: 1 to 276 days). Rash leading to dose reduction occurred in 5% of patients, and RYBREVANT was permanently discontinued due to rash in 0.7% of patients. 

Toxic epidermal necrolysis occurred in one patient (0.3%) treated with RYBREVANT. 

Instruct patients to limit sun exposure during and for 2 months after treatment with RYBREVANT. Advise patients to wear protective clothing and use broad spectrum UVA/UVB sunscreen. Alcohol free emollient cream is recommended for dry skin. 

If skin reactions develop, start topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. Withhold, dose reduce or permanently discontinue RYBREVANT based on severity.

Ocular Toxicity
RYBREVANT can cause ocular toxicity including keratitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, and uveitis. Based on the safety population, keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients treated with RYBREVANT. All events were Grade 1-2. Promptly refer patients presenting with eye symptoms to an ophthalmologist. Withhold, dose reduce or permanently discontinue RYBREVANT based on severity. 

Embryo Fetal Toxicity
Based on its mechanism of action and findings from animal models, RYBREVANT can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment and for 3 months after the final dose of RYBREVANT. 

Adverse Reactions
The most common adverse reactions (≥20%) were rash, IRR, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation, and vomiting. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased albumin, decreased phosphate, decreased potassium, increased alkaline phosphatase, increased glucose, increased gamma-glutamyl transferase, and decreased sodium. 

On March 29, 2023 Broncus Medical (02216.HK), a leader in precise interventional diagnosis and therapy of lung diseases in China, reported its annual results for the year ended December 31, 2022 (Press release, Broncus Technologies, MAR 29, 2023, View Source [SID1234629514]). During the period, despite the disturbance of external adverse factors such as global instability, repeated overlap of the COVID-19 pandemic in China and periodic downward trend of industry prosperity, the company steadfastly focused on the development strategy of providing innovative interventional diagnosis and treatment solutions for lung diseases worldwide, actively boosted the innovative R&D on diagnostic and therapeutic consumables products and the upgrades of lung navigation products. Moreover, the company accelerated the pace of channel underlaying and commercialization empowerment, and promoted its business to fulfill an integrated development in multiple categories. As a result, the company achieved positive product sales growth in 2022.

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In 2022, Broncus Medical earned product sales of US$9.41 million, an increase of 8% compared to the same period in 2021. Of which, total revenue from Mainland China was US$5.81 million, a significant increase of 50% compared to the same period in 2021. Gross profit was US$7.32 million, with the gross margin at 78%. US$19.17 million was spent on Broncus Medical R&D in fiscal 2022, an increase of 14% compared to the same period in 2021.

Innovative products accessing to global markets are processing smoothly

As of December 31, 2022, the company had 18 major product candidates under various development stages, of which, several products made breakthroughs in global market access and commercialization, including:

(1) In March 2022, the company’s InterVapor was approved by the National Medical Products Administration of China (NMPA), denoting the official commercialization in China;

(2) BioStarNeedle, a disposable endoscope suction biopsy needle, was approved in the European Union in September 2022.

(3) In October 2022, "Mist Fountain", the company’s disposable nebulizing micro-catheter for endoscope, was approved for marketing in China;

(4) In March 2023, our six products, namely LungPoint, Archimedes, Lungpoint Plus, and Arhchimedes Access Kit (Flexneedle, Sheath and Balloon), were officially approved for marketing by MD-15 regulations of the India authorities.

Specifically, the "Mist Fountain" nebulizing micro-catheter is used in conjunction with the endoscope. Under the guidance of the navigation system, it can accurately reach the lesion site, atomize and administer the drug, and directly deliver the drug to the lung lesion tissue. The product has strong compatibility and multiple indications. It is compatible with many kinds of drugs and is mainly used for accurate anti-inflammation, local hemostasis, phlegm reduction and elimination, staining location, local anesthesia, etc. In the future, the company will cooperate with clinical experts and biopharmaceutical enterprises to promote, amongst others, the possible application of the nebulizing micro-catheter in the anesthesia of bronchoscopy surgery, tuberculosis treatment, targeted drug delivery for oncology. In addition, the company will continue to explore possible usage scenarios of the Product to cover a wider range of lung disease treatments in order to consolidate leading advantages of the company in the field of precision interventional diagnosis and treatment of pulmonary diseases.

Based on the progress in the global access sector, the company relied on experiences of marketed products to comprehensively integrate the sales channels of diversified product lines, so as to continuously empower the commercialization of the company’s products at various stages.

Leading advantages of the company’s lung disease treatment products continue to consolidate, while product commercialization is steadily advancing.

Navigation products

The company currently has three marketed navigation products, including LungPoint, LungPoint Plus (known as "Archimedes Lite" outside Asia) and LungPro (known as "Archimedes" outside China). As the only global provider of enhanced reality navigation technology for the whole lung through the bronchus, Broncus Medical has provided real-time navigation in the airway for lung surgeries, thereby more accurately and effectively planning the path to the lesion. The commercialization of navigation products has been steadily promoted via a combination of direct sales and distribution. Although constantly impacted by the pandemic, navigation products ranked first in China’s installed market share in 2022 according to market public information.

InterVapor

InterVapor is the world’s first and only Thermal Vapor Treatment System to treat COPD. In March 2022, InterVapor was approved by NMPA. In July, the first clinical applications of InterVapor were completed in Guangdong Province and Shaanxi Province after the approval for marketing in China, and the clinical applications were quickly carried out in Liaoning Province, Beijing City and other places, thus significantly benefiting the patients. Currently, the Product is steadily implemented in pricing, procurement and admission processes in China, while being applied for marketing in the US, the Philippines and Malaysia.

RF-II

RF-II is a radiofrequency ablation system used in conjunction with a disposable lung radiofrequency ablation catheter. The company completed enrollment for registered clinical trial for RF-II radiofrequency ablation system in December 2021. The data related to its main clinical endpoints are currently being evaluated, and the product is scheduled to be submitted to NMPA for a registration approval. In addition, the corresponding doctor training and an application for the US 510K license as well as the European CE Mark related to the product are also in the preparation process.

TLD

TLD, a Targeted Lung Denervation product, is the first product independently developed by China for the treatment of COPD by transbronchial radiofrequency ablation, which can be used for up to 51.6% of the patients with COPD. In July 2022, the company completed the enrollment of all subjects for the clinical trial of the first application of the TLD radiofrequency ablation system in the human body. All subject follow-up visits will be completed in July 2023. The clinical trial report for the study is expected to be published by the end of 2023. The company successfully held a meeting to discuss the clinical trial investigator protocol for the project in November 2022, and the clinical study was reviewed by the Ethics Committee of West China Hospital in February 2023, signifying an official launch of its registered clinical study, which is a prospective, randomized, single-blind, sham-operated group-controlled multicenter clinical trial.

The company remains in the industry’s leading position in technical advantages of its core therapeutic products. In the future, the company aims to develop more therapeutic products based on the navigation platform, in a bid to unswervingly provide "Broncus Solution" targeting respiratory intervention therapies for lung diseases worldwide.

Product R&D capability advance at an equal pace with patent protection

In terms of R&D, Broncus Medical focuses on developing innovative technologies and products for lung navigation and diagnosis and treatment. Its R&D mode that combines international leading technology advantages with local R&D cost advantages has greatly supported the company’s product innovation.

As of December 31, 2022, we obtained 748 patents and patent applications which consisted of 359 issued patents (including pending announcements) and 198 patent applications in China and 105 issued patents and 86 patent applications overseas including key markets such as the U.S. and the EU. Among the patents obtained, 117 and 50 of them are related to InterVapor and RF-II, respectively.

As of December 31, 2022, the company had 18 major product candidates under various development stages, which were jointly researched, developed and updated by the R&D center teams from China and the U.S. Meanwhile, the company supported its intellectual property portfolio and product iteration by participating in government scientific research projects, such as the 2022 "Leading Goose" R&D Program in Zhejiang Province.

Diversified strategic cooperation enables the company’s business to achieve healthy and sustainable development

In February 2022, Broncus Medical entered into a strategic cooperation agreement with Healium Medical Ltd. ("Healium"), an Israeli company specializing in the development of ultrasound energy therapy and imaging monitoring. The cooperation aims to integrate energy ablation and ultrasound technology, so that the operator can realize real-time monitoring of the state of ablated tissues without frequently changing devices, thus effectively avoiding insufficiency or excess of energy in the treatment process, promoting the predictability of treatment results, simplifying the operation, improving the safety and effectiveness of the operation, and the popularization of interventional surgery in the treatment of lung diseases. The cooperation was approved by Israel IIA and the input and output confirmation of R&D design was officially initiated in May 2022.

In July 2022, Broncus Medical and Shanghai United Family Healthcare jointly established the "MultiDisciplinary Diagnostics of Pulmonary Nodules", to cover the population with high-end commercial insurance. This is the first step in the strategic cooperation between the parties. In the future, the parties will continue to jointly explore new models of respiratory intervention diagnosis and treatment services as well as other cutting-edge technologies for groups with high-end medical needs.

In November 2022, Broncus Medical entered into a strategic partnership with Eternal Asia, a leading enterprise in supply chain services in China, so as to give full play to the core advantages of the parties, integrate resources through a cooperation platform, complement each other’s advantages, and enhance competitiveness. Eternal Asia will use its professional supply chain services to facilitate the coverage of Broncus pulmonary intervention diagnosis and treatment products over a wider market.

In December 2022, Broncus Medical signed a strategic cooperation agreement on medical-engineering integration, with Guangzhou Institute of Respiratory Health with regard to the lung radio frequency ablation system project & the adjustable and bendable bronchoscope sheath project. Based on their respective advantages in medical resources and technology platforms, the parties will establish a comprehensive, wide-coverage and diversified cooperation system, to actively promote the deep integration and technological innovation of medicine and engineering, and usher in a new era of interventional therapy for lung cancer.

Since December 2022, Broncus Medical signed a partnership agreement for the digital medical innovation center with AstraZeneca. During the cooperation, the integrated diagnosis and treatment products can be displayed in the digital medical innovation center of AstraZeneca in Hangzhou. The parties will also jointly participate in a series of training activities of the Respiratory Intervention Training College.

Localized production enhances gross profit margin and commercialization

Three navigation products released by Broncus Medical were all produced by a factory in San Jose, California in the U.S. The domestic LungPoint, received a correction notice from NMPA in October 2022, is expected to be approved for marketing in May 2023. The domestic LungPro is expected to obtain an approval in September 2023.

Since 2021, Broncus Medical’s plant in Hangzhou has gradually become a key site to produce the company’s entire range of products, including InterVapor . The move will promote the company to achieve localized production, reduce costs and increase efficiency, further expand the gross profit margin of its products, and penetrate its products into more hospitals based on aligning with the company’s product promotion strategy and policy guidance.

International sales layout and continuous surgery-oriented popularization

Adopting a combination of direct sales and distribution, Broncus Medical sold its products to 33 countries and regions all over the world, including the United States, the United Kingdom, Germany, France, Japan, etc. By leveraging its more established experience in marketing of its navigation system, Broncus Medical plans to expand its sales of products worldwide.

In terms of the surgical popularization, Broncus Medical plans to provide more doctor training and patient education services. Through the proprietary Bronchoscopic Transparenchymal Nodule Access (BTPNA) technology, the company will enhance the understanding of hospitals, doctors and patients about the navigation platform as an indispensable tool for respiratory interventional disease diagnosis and treatment. Superimposing the R&D and commercialization of a range of therapeutic products, the company aims to penetrate its products to into more hospitals, offering continuous impetus for the growth of its sales.

Under the overlapped heavy pressures like demand shrinking, the epidemic impact and tensioned international relations, Broncus Medical made full use of market functions to fully promote the product pricing, cost control and R&D investment, achieving a growth in product sales and demonstrating strong business resilience and growth potential in 2022.