On March 29, 2023 CollPlant Biotechnologies (Nasdaq: CLGN), a regenerative and aesthetics medicine company developing innovative technologies and products based on its non-animal-derived collagen for tissue regeneration and organ manufacturing, reported financial results for the full year ended December 31, 2022 and provided a corporate update on its programs (Press release, CollPlant, MAR 29, 2023, View Source [SID1234629519]).

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Yehiel Tal, CollPlant’s Chief Executive Officer, stated, "We remain highly focused on becoming a global leader in regenerative medicine with our pioneering collagen-based platform to help people live longer and better. Towards this goal, we have been advancing our programs and recently announced successful completion of a preclinical study of our 3D bioprinted regenerative breast implants, that would address the $2.6 billion global breast implant market, and, importantly, offer an alternative with an improved safety profile. In addition, we are pleased to have recently announced encouraging data from a 12-month preclinical study of our proprietary, paradigm-shifting photocurable dermal and soft-tissue filler, which demonstrated superior tissue regeneration, lifting capacity and volume retention when compared to a commercial standard. We believe this product candidate has the potential to be highly competitive by providing both refined aesthetic results as well as uniquely regenerative benefits. CollPlant has granted its global pharmaceutical partner, AbbVie, the right of first negotiation to obtain a worldwide exclusive license to this product."

Mr. Tal, continued, "Furthermore, we expanded our bioinks product portfolio adding recombinant human collagen-based ink products with very competitive features for the end-user. Our portfolio of bioink products is yet another category where we believe that we can deliver clear and distinct advantages, including biofunctionality, homogeneity and safety. We are confident that our collaboration with a worldwide pharmaceutical leader as well as other numerous collaborations and partnership agreements has validated our technology and its multiple areas of applicability, and remain in discussions with several other industry leaders for partnership opportunities. We look forward to a communicating our additional progress and a promising remainder this year."

Q4 and recent corporate highlights

Program development

In January 2023, CollPlant announced that it successfully completed a large-animal study for its 3D bioprinted regenerative breast implants. The preclinical study demonstrated progressive stages of tissue regeneration after three months, as highlighted by the formation of maturing connective tissue and neovascular networks within the implants, with no adverse events reported. Based on these positive results, the Company is planning to initiate a follow-up, large-animal study in the second half of 2023 using commercial-size implants to support subsequent human studies and future product commercialization.
In the U.S. alone, Hundreds of thousands of people per year experience adverse events that range from autoimmune symptoms to the very serious breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). CollPlant’s breast implants that are comprised of the Company’s proprietary plant-derived rhCollagen and other biomaterials, are expected to regenerate breast tissue without eliciting immune response, and thus may provide a revolutionary alternative for aesthetic and reconstructive procedures, including postmastectomy for cancer patients.
Also, during 2022, CollPlant completed a long-term, pivotal preclinical study to advance the development of its third-generation photocurable dermal and soft-tissue filler. This dermal filler is the first injectable photocurable regenerative soft tissue filler being developed or use in aesthetic medicine. It is based on a holistic platform technology which combines the properties of rhCollagen with hyaluronic acid creating a contouring effect. The 12-month study results demonstrated superior tissue regeneration, lifting capacity and volume retention when compared to the industry gold standard. These promising results, combining the regenerative properties of collagen and the advantages of the photocuring technology, position CollPlant closer towards being able to offer a revolutionary platform technology, that has the potential to create a paradigm shift in the evolving medical aesthetic market.
Collaboration updates

In November of 2022, CollPlant announced entering into a license and research agreement together with Ramot, the Technology Transfer Company of Tel Aviv University and Sheba Medical Center, a hospital ranked by Newsweek magazine as one of the Top 10 world best hospitals for the 4th consecutive year (2019-2022). All entities are in collaboration to co-develop a ‘Gut-on-a-Chip’ tissue model for drug discovery and high throughput screening of drugs The model is intended to be used in personal medicine applications for the treatment of ulcerative colitis, an inflammatory bowel disease affecting millions of individuals worldwide. The in-vitro intestine-on-chip platform combines CollPlant’s rhCollagen with other proprietary biomaterials and human cells. Designed to emulate the human intestine tissue, the 3D bioprinted model will allow medical professionals to identify drug targets and personalized therapeutic responses that can lead to improved patient outcomes.
CollPlant has the potential to receive additional milestone payments as well as future royalties in accordance with its long-term collaboration with AbbVie for its first-generation dermal filler, and CollPlant expects that the first of these milestones could be achieved in 2023. CollPlant remains engaged in partnering discussions with several industry leaders and academic institutions interested in the Company’s rhCollagen technology and expertise in 3D bioprinting to develop therapeutics and medical applications.
Commercial portfolio of bioink solutions

In November 2022 and in January 2023, CollPlant expanded its commercial portfolio of rhCollagen-based bioinks adding two new products: Collink.-3D 90 and Collink.-3D 50L, respectively. Collink.-3D 90 offers increased mechanical properties, while Collink.3D 50L is the first bioink available in powder form which provides enhanced operational flexibility for the end-user.
– Collink-3D 90 is a complement to the Company’s first commercial bioink, Collink-3D 50, which was launched late last year, and offers more mechanical properties to address additional printing requirements of soft and hard tissues.
– Collink.-3D 50L is a tunable bioink that can be easily reconstituted to form solutions with application-specific concentrations, as well as formulated with other components and crosslinked to form hydrogels that meet the demand for specific geometric, physical and biological properties of different 3D constructs.
Fundamental optionality is expanded with these new bioinks since they will enable both specificity and flexibility for the end user for use in a wide range of 3D bioprinting applications, including drug discovery, drug screening and tissue testing, as well as the development of transplantable tissues and organs.

Intellectual property developments

During 2022, CollPlant developed a proprietary aseptic process to mass-produce sterile recombinant human collagen. This is a first-of-its-kind, non-animal-derived collagen that will allow for production flexibility with partners.

Year ended December 31, 2022 financial results

Cash, cash equivalents and short-term deposits as of December 31, 2022, were $29.7 million (excluding restricted cash).

GAAP revenue for the year ended December 31, 2022, was $0.3 million and included income from sales of the Company’ BioInk and rhCollagen. Revenues decreased by $15.3 million, compared to $15.6 million in the year ended December 31, 2021. The decrease resulted mainly from the $14 million upfront payment received from AbbVie in 2021.

GAAP cost of revenue for the year ended December 31, 2022, was $0.4 million, a decrease of 80% compared to $2.0 million in the year ended December 31, 2021. Cost of revenue includes mainly the cost of the Company’s rhCollagen-based BioInk products, and royalties to the Israel Innovation Authority, or IIA, for the Company’s sales. The decrease in cost of revenue in the amount of approximately $1.6 million is mainly comprised of: (i) a decrease of approximately $460,000 in royalty expenses to the IIA and (ii) a decrease in the amount of approximately $1.0 million relating to BioInk and rhCollagen sales.

GAAP gross loss for the year ended December 31, 2022 was $0.1 million, a decrease of $13.5 million compared to gross profit of $13.6 million in the year ended December 31, 2021.

GAAP operating expenses for the year-ended December 31, 2022, were $17.0 million, compared to $13.6 million in the year ended December 31, 2021. The increase in expenses amounting to approximately $3.4 million is mainly comprised of: (i) $1.4 million in research and product development activities including process development, (ii) $1.0 million in employees’ salaries and share base compensation, including recruitment of new employees for development of new products in 3D bioprinting and medical aesthetics, and (iii) an increase of $0.9 million in general and administrative employees and directors salaries and insurance policy expenses. On a non-GAAP basis, the operating expenses for the year ended December 31, 2022 were $15.2 million, compared to $11.9 million for the year ended December 31, 2021. Non-GAAP measures exclude certain non-cash expenses.

GAAP financial income, net for each of the years ended December 31, 2022 and 2021 totaled $172,000. Financial income net is mainly attributed to interest received from the Company’s short-term cash deposits.

GAAP net loss for the year ended December 31, 2022 was $16.9 million, or $1.53 basic loss per share, compared to a net income of $237,000, or $0.02 income per share, for the year ended December 31, 2021. Non-GAAP net loss the year ended December 31, 2022 was $15.2 million, or $1.37 basic loss per share, compared to $1.9 million income, or $0.19 basic income per share, for the year ended December 31, 2021.

Cash used by operating activities during the year 2022, was $13.7 million compared to $2.5 million cash provided by operating activities in the year 2021.

Cash provided by investing activities during the year 2022, was $28.9 million compared to $31.6 million cash used in the year 2021. The decrease is mainly attributed to repayment and investment in short-term cash deposits.

Cash provided by financing activities during the year 2022 was $1.9 million compared to cash provided in financing activities of $38.8 million in the year 2021. In 2022, the Company received $1.9 million mainly from the exercise of warrants into the Company’s shares. In 2021, the Company completed a registered direct offering, which resulted in net proceeds of $32 million, and, in addition, had proceeds in the amount of $6.0 million from exercise of options and warrants.

Conference call information

CollPlant will hold a conference call to discuss its full and year and fourth quarter 2022 financial results along with corporate updates on March 29th at 10 am ET. To participate in the conference call, please use the dial-in information below:

U.S. investors: 1-877-407-9716
Israel investors toll-free number: 1 809 406 247
Other investors outside of the U.S.: 1-201-493-6779
Conference ID: 13736701

Note, you can avoid long wait times for the operator by using the Call me feature and clicking the link below 15 minutes prior to the scheduled call start time:

View Source;passcode=13728588&h=true&info=company&r=true&B=6

To participate in listen-only mode, and to view slides corresponding to the Company’s conference call, please visit the News & Events section of the CollPlant Investor Relations website.

COLLPLANT BIOTECHNOLOGIES LTD.

CONDENSED CONSOLIDATED BALANCE SHEETS

(U.S. dollars in thousands)

December 31,

2022

2021

Assets

Current assets:

Cash and cash equivalents

$

29,653

$

13,148

Short term cash deposits

–

30,151

Restricted deposit

23

13

Trade receivables

9

270

Other accounts receivable and prepaid expenses

543

424

Inventories

1,430

1,081

Total current assets

31,658

45,087

Non-current assets:

Restricted deposit

188

213

Operating lease right-of-use assets

2,711

2,953

Property and equipment, net

2,966

2,728

Intangible assets

245

243

Total non-current assets

6,110

6,137

Total assets

$

37,768

$

51,224

COLLPLANT BIOTECHNOLOGIES LTD.

CONDENSED CONSOLIDATED BALANCE SHEETS

(U.S. dollars in thousands, except share data)

December 31,

2022

2021

Liabilities and shareholders’ equity

Current liabilities:

Trade payables

$

1,133

$

1,034

Operating lease liabilities

529

519

Deferred revenues

–

32

Accrued liabilities and other

1,443

1,429

Total current liabilities

3,105

3,014

Non-current liabilities:

Operating lease liabilities

2,382

3,089

Total non-current liabilities

2,382

3,089

Total liabilities

5,487

6,103

Commitments and contingencies

Shareholders’ Equity:

Ordinary shares, NIS 1.5 par value – authorized: 30,000,000 ordinary shares
as of December 31, 2022 and December 31, 2021; issued and
outstanding: 11,186,481 and 10,772,024 ordinary shares as of
December 31, 2022 and December 31, 2021, respectively

4,873

4,664

Additional paid in capital

118,099

114,223

Currency translation differences

(969)

(969)

Accumulated deficit

(89,722)

(72,797)

Total shareholders’ equity

32,281

45,121

Total liabilities and shareholders’ equity

$

37,768

$

51,224

COLLPLANT BIOTECHNOLOGIES LTD.

CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS

(U.S. dollars in thousands, except share and per share data)

Year ended December 31,

2022

2021

2020

Revenues

$

299

$

15,641

$

6,137

Cost of revenues

400

2,005

3,002

Gross Profit (loss)

(101)

13,636

3,135

Operating expenses:

Research and development, net

10,255

7,631

4,065

General, administrative and marketing

6,741

5,940

4,669

Total operating income (loss)

(17,097)

65

(5,599)

Financial income (expenses), net

172

172

(175)

Net income (loss)

$

(16,925)

$

237

$

(5,774)

Basic net income (loss) per ordinary share

(1.53)

0.02

(0.84)

Diluted net income (loss) per ordinary share

(1.53)

0.02

(0.84)

Weighted average ordinary shares outstanding used in
computation of basic net income (loss) per share

11,033,310

9,968,972

6,886,955

Weighted average ordinary shares outstanding used in
computation of diluted net income (loss) per share

11,033,310

11,966,788

6,886,955

COLLPLANT BIOTECHNOLOGIES LTD.

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS

(U.S. dollars in thousands)

2022

2021

2020

Cash flows from operating activities:

Income (loss)

$

(16,925)

$

237

$

(5,774)

Adjustments for:

Depreciation

1,076

773

660

Gains from Short term cash deposits

(87)

(151)

–

Share-based compensation to employees and consultants

2,174

1,597

1,674

Exchange differences on cash and cash equivalents

608

(143)

(60)

Financial expenses (income) related to financial instruments

–

(28)

(40)

Changes in operating asset and liability items:

Decrease (increase) in trade receivables

261

560

(751)

Decrease (increase) in inventories

(312)

181

(374)

Decrease (increase) in other receivables

(119)

(185)

31

Decrease in operating right of use assets

461

400

442

Increase (decrease) in trade payables

99

236

(35)

Decrease in lease liabilities

(916)

(337)

(229)

Increase (decrease) in accrued liabilities and other payables

14

(464)

740

Decrease in deferred revenues (including long term deferred revenues)

(32)

(175)

(735)

Net cash provided by (used in) operating activities

(13,698)

2,501

(4,451)

Cash flows from investing activities:

Capitalization of intangible assets

(42)

(161)

(82)

Purchase of property and equipment

(1,274)

(1,428)

(437)

Repayment of a short term deposits

50,238

–

–

Investment in short term deposits

(20,000)

(30,000)

–

Proceeds from sale of property and equipment

–

33

–

Net cash provided by (used in) investing activities

28,922

(31,556)

(519)

Cash flows from financing activities:

Proceeds from issuance of shares and warrants less issuance expenses

–

32,743

4,400

Exercise of options and warrants into shares

1,874

6,017

89

Loan repaid

–

–

(24)

Net cash provided by financing activities

1,874

38,760

4,465

Increase (Decrease) in cash and cash equivalents and restricted deposits

17,098

9,705

(505)

Exchange differences on cash and cash equivalents and restricted deposits

(608)

143

60

Cash and cash equivalents and restricted deposits at the beginning of the year

13,374

3,526

3,971

Cash and cash equivalents and restricted deposits at the end of the year

$

29,864

$

13,374

$

3,526

COLLPLANT BIOTECHNOLOGIES LTD.

APPENDICES TO CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS

(U.S. dollars in thousands)

Year ended December 31,

2022

2021

2020

Appendix to the statement of cash flows

A. Supplementary information on investing and financing activities not involving cash flows:

Conversion of pre-paid warrants to ordinary shares

–

–

355

Obtaining right of use assets in exchange for a lease liability

219

557

23

Classification of issuance costs liability to equity

–

50

–

Capitalization of Share-based compensation to inventory

37

–

–

B. Reconciliation of Cash, cash equivalents and restricted cash at the end of the year

Cash and cash equivalents

29,653

13,148

3,333

Restricted deposits short term

23

13

12

Restricted deposits long term

188

213

181

Total cash and cash equivalents and restricted deposits

$

29,864

$

13,374

$

3,526

CollPlant Biotechnologies Ltd.

Reconciliation of GAAP to Non-GAAP Financial Measures

(U.S. dollars in thousands, except per share data)

(Unaudited)

Year ended December 31,

2022

2021

USD in thousands

GAAP gross profit (loss)

$

(101)

$

13,636

GAAP operating costs and expenses:

16,996

13,571

Change of operating lease accounts

455

(63)

Share-based compensation to employees, directors and consultants

(2,211)

(1,597)

Non-GAAP operating costs and expenses:

15,240

11,911

GAAP operating income (loss)

(17,097)

65

Non-GAAP operating income (loss)

(15,341)

1,725

GAAP net income (loss)

(16,925)

237

Change in fair value of financial instruments

–

(28)

Change of operating lease accounts

(455)

63

Share-based compensation to employees, directors and consultants

2,211

1,597

Non-GAAP net income (loss)

$

(15,169)

$

1,869

GAAP Basic net income (loss) per ordinary share

$

(1.53)

$

0.02

GAAP diluted net income (loss) per ordinary share

(1.53)

0.02

Non-GAAP Basic net income (loss) per ordinary share

$

(1.37)

$

0.19

Non-GAAP diluted net income (loss) per ordinary share

(1.37)

0.16

References

1 View Source

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.