Nuvalent to Present New Preclinical Data on ALK-Selective Inhibitor NVL-655 at AACR Annual Meeting 2023

On March 14, 2023 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported an upcoming preclinical data poster presentation supporting the ongoing clinical development of its ALK-selective inhibitor, NVL-655 (Press release, Nuvalent, MAR 14, 2023, View Source [SID1234628710]). The data, resulting from a collaboration with the Yonsei University College of Medicine, will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, taking place April 14-19 in Orlando, Florida.

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The poster describes the preclinical intracranial antitumor activity of NVL-655 in a brain-implanted xenograft model derived from a patient with lung cancer harboring the alectinib-resistant EML4-ALK v3 G1202R mutation. The poster additionally expands the characterization of NVL-655 alongside other ALK inhibitors. NVL-655 has previously demonstrated intracranial efficacy in a cell line-derived xenograft model as well as broad preclinical activity across diverse ALK resistance mutations and tumor types while maintaining high selectivity for ALK over TRKB. NVL-655 is currently being investigated in the ALKOVE-1 study (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors.

The poster will be archived on the Nuvalent website at www.nuvalent.com following the presentation.

Details for the poster presentation are as follows:

Title: Preclinical intracranial activity of NVL-655 in an alectinib-resistant patient-derived model harboring EML4-ALK fusion with G1202R mutation
Authors: Jii Bum Lee*1, Mi Ra Yu*1, Mi Ran Yun1, You Won Lee1, Seung Yeon Oh1, Eun Ji Lee1, Anupong Tangpeerachaikul2, Henry E. Pelish2, Byoung Chul Cho1
Presenter: Anupong Tangpeerachaikul, Ph.D.
Permanent Abstract: 4022
Session Category: Experimental and Molecular Therapeutics
Session Title: Tyrosine Kinase and Phosphatase Inhibitors 1
Session Date and Time: Tuesday April 18, 2023 from 9:00 a.m. – 12:30 p.m. ET
Location: Orange County Convention Center, Poster Section 20
1Yonsei University College of Medicine, Seoul, Republic of Korea 2Nuvalent Inc., Cambridge, MA, USA
*Equal contributions

About NVL-655

NVL-655 is a novel brain-penetrant ALK-selective inhibitor created to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with the solvent front G1202R mutation or compound mutations G1202R / L1196M ("GRLM"), G1202R / G1269A ("GRGA"), or G1202R / L1198F ("GRLF"). NVL-655 has been optimized for CNS penetrance to improve treatment options for patients with brain metastases. NVL-655 has been observed in preclinical studies to selectively inhibit wild-type ALK and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and drive more durable responses for patients. NVL-655 is currently being investigated in the ALKOVE-1 study (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors.

PAVmed Provides Business Update and Preliminary Fourth Quarter and Full Year 2022 Financial Results

On March 14, 2023 PAVmed Inc. (NASDAQ: PAVM, PAVMZ) ("PAVmed" or the "Company"), a diversified commercial-stage medical technology company, operating in the medical device, diagnostics, and digital health sectors, reported a business update for the Company and its subsidiaries, Lucid Diagnostics Inc. (NASDAQ: LUCD) ("Lucid") and Veris Health Inc. ("Veris"), and presented financial results for the year ended December 31, 2022 (Press release, PAVmed, MAR 14, 2023, View Source [SID1234628709]).

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Conference Call and Webcast

The webcast will be available at the investor relations section of the Company’s website at pavmed.com. Alternatively, to access the conference call by telephone, U.S.-based callers should dial 877-550-1858 and international listeners should dial 1-848-488-9160. All listeners should provide the operator with the conference call name "PAVmed, Inc. Business Update Conference Call" to join.

Those seeking further details on Lucid are encouraged to visit the company’s website at luciddx.com to view the webcast of its business update call held yesterday, and its corresponding press release.

Business Update Highlights

"Over the past two months, the PAVmed team has executed on its strategic restructuring plan to protect long-term shareholder interests during challenging market conditions by tightly focusing its efforts and resource allocation on near-term commercial activities and milestones," said Lishan Aklog, M.D., PAVmed’s Chairman and Chief Executive Officer. "The plan is working and appears to have been right-sized—extending cash runway while assuring the commercial efforts are adequately resourced. Lucid continues to deliver steady EsoGuard test volume growth through organic sales and now high-volume testing events and is gaining traction with commercial payors. Veris’ momentum is accelerating with an exciting commercial product, strong customer interest and a powerful business model which is not dependent on securing third-party reimbursement. I am proud how the team has battled through these challenges and emerged stronger with a bright commercial future for what remains a diversified portfolio."

Highlights from the fourth quarter and recent weeks include:

In January 2022, PAVmed launched a strategic restructuring initiative designed to maximize cash runway and protect long-term shareholder interests through adjustments in near-term strategic priorities and associated resource allocation. The Company stated that it would focus substantially all its resources and near-term efforts on accelerating the commercialization of Lucid’s and Veris’ products, resulting in a meaningful reduction in its workforce and quarterly cash burn. The strategic initiative has been completed resulting in a durable, positive impact on the consolidated cash runway and balance sheet, which were further strengthened by Lucid’s announcement yesterday that it had secured $24.6 million in financing extending its cash runway well into 2024.

In December 2022, Veris, PAVmed’s digital health subsidiary, focused on enhancing personalized cancer care through remote patient monitoring (RPM), commercially launching its Veris Cancer Care Platform ("Veris CCP"), and executing its first commercial contract with New Jersey Cancer Care, PA ("NJCC"), a leading oncology practice and member of the prestigious Quality Cancer Care Alliance.

In February 2023, the Veris Cancer Care Platform (Veris CCP) went live following successful onboarding of the first cohort of cancer patients and their clinicians. Enrolled patients received a VerisBox and began connecting their Bluetooth-enabled health care devices to transmit real-time physiologic data to the cloud-based Veris CCP clinician portal. The patients also began reporting symptoms and quality-of-life parameters through the Veris CCP patient smartphone app, which became available for patients on the Apple App Store and Google Play. The cloud-based clinician portal was integrated into the oncology practice and the cancer care team began using it to review physiologic and clinical data and other RPM services for which they can bill. The software-as-a-service recurring-revenue business model is now poised to deliver near-term value at attractive margins to both Veris and its clients.

Veris is now focused on optimizing the patient and clinician experience, achieving high patient compliance, and streamlining the integration processes as its commercial team drives adoption and delivers new accounts. Feedback and interest in Veris CCP from oncology practices and cancer care centers is strong, focusing on Veris CCP as tool to enhance personalized care and as well as practice economics through RPM.

Veris has made steady progress on development and regulatory milestones for its implantable physiologic monitor and is targeting a commercial launch next year. The device, which is designed to be implanted in conjunction with a chemotherapy vascular access port, will further the power of the Veris CCP platform by assuring near perfect patient compliance with RPM data reporting requirements.

Yesterday, Lucid provided a detailed update of its commercial and financial performance. Quarterly EsoGuard testing volume continues along a steady growth path, both sequentially and annually. Satellite Lucid Test Center (sLTC) activity, whereby Lucid clinicians collect samples at physician offices, continues to increase rapidly, with Lucid clinicians now performing the majority of cell collection procedures either in an LTC or sLTC.

Lucid’s commercial payor engagement is accelerating, particularly with its signing of an in-network agreement with MultiPlan, the largest secondary Preferred Provider Organization (PPO), expanding EsoGuard’s access to include Multiplan’s estimated 60 million consumers. EsoGuard pricing is holding, with in-network contracts, averaging more than $2000 per test and all in-network PPO contracts priced at or above the Medicare payment rate of $1938. Key drivers of future in-network commercial payor contracting—generating claims history with individual payors and collecting retrospective and prospective clinical utility data—are also progressing well.

Lucid continues to expand its commercial horizons bringing EsoGuard testing directly to at-risk patients at high-volume testing day events and launching a direct contracting strategic initiative to engage directly with large Administrative Services Only (ASO) self-insured employers, unions, and other entities.
Financial Results

For the fourth quarter of 2022, EsoGuard related revenues were $0.1 million while for the year ended December 31, 2022, revenues were $0.4 million. Fourth-quarter and full-year 2022 operating expenses were approximately $24.6 million and $91.3 million, respectively, which include stock-based compensation expenses of $4.9 million and $19.5 million, respectively. GAAP net loss attributable to shareholders for the fourth quarter and full-year 2022 were approximately $20.5 million and $89.2 million, or $(0.23) and $(1.00) per common share.

As shown below and for the purpose of illustrating the effect of stock-based compensation and other non-cash income and expenses on the Company’s financial results, the Company’s preliminary non-GAAP adjusted loss for the fourth quarter and year ended December 31, 2022, were approximately $13.8 million and $54.0 million or $(0.15) and $(0.61) per common share.

PAVmed had cash and cash equivalents of $39.7 million as of December 31, 2022, compared with $77.3 million as of December 31, 2021.
PAVmed Non-GAAP Measures

To supplement our unaudited financial results presented in accordance with U.S. generally accepted accounting principles (GAAP), management provides certain non-GAAP financial measures of the Company’s financial results. These non-GAAP financial measures include net loss before interest, taxes, depreciation, and amortization (EBITDA) and non-GAAP adjusted loss, which further adjusts EBITDA for stock-based compensation expense, loss on the issuance or modification of convertible securities, the periodic change in fair value of convertible securities, and loss on debt extinguishment. The foregoing non-GAAP financial measures of EBITDA and non-GAAP adjusted loss are not recognized terms under U.S. GAAP.

Non-GAAP financial measures are presented with the intent of providing greater transparency to the information used by us in our financial performance analysis and operational decision-making. We believe these non-GAAP financial measures provide meaningful information to assist investors, shareholders, and other readers of our unaudited financial statements in making comparisons to our historical financial results and analyzing the underlying performance of our results of operations. These non-GAAP financial measures are not intended to be, and should not be, a substitute for, considered superior to, considered separately from, or as an alternative to, the most directly comparable GAAP financial measures.

Non-GAAP financial measures are provided to enhance readers’ overall understanding of our current financial results and to provide further information for comparative purposes. Management believes the non-GAAP financial measures provide useful information to management and investors by isolating certain expenses, gains, and losses that may not be indicative of our core operating results and business outlook. Specifically, the non-GAAP financial measures include non-GAAP adjusted loss, and its presentation is intended to help the reader understand the effect of the loss on the issuance or modification of convertible securities, the periodic change in fair value of convertible securities, the loss on debt extinguishment and the corresponding accounting for non-cash charges on financial performance. In addition, management believes non-GAAP financial measures enhance the comparability of results against prior periods.

A reconciliation to the most directly comparable GAAP measure of all non-GAAP financial measures included in this press release for the three months and year ended December 31, 2022, and 2021 is as follows:

For the three months
ended December 31,

For the year ended
December 31,

2022

2021

2022

2021

Revenue

$ 112

$ 300

$ 377

$ 500

Operating expenses

24,616

19,979

91,304

54,893

Other (Income) Expense

68

12,311

1,733

Net Loss

24,572

19,679

103,238

56,126

Net income (loss) per common share, basic and diluted

$ (0.23)

$ (0.21)

$ (1.00)

$ (0.42)

Net loss attributable to common stockholders

(20,532)

(17,285)

(89,264)

(50,630)

Preferred Stock dividends and deemed dividends

71

67

281

283

Net income (loss) as reported

(20,461)

(17,218)

(88,983)

(50,347)

Adjustments

Depreciation and amortization expense1

1,426

198

2,457

226

Interest expense, net

223

1,272

53

EBITDA

(18,812)

(17,020)

(85,254)

(50,068

Other non-cash or financing related expenses

Stock-based compensation expense2

4,949

4,380

19,532

15,009

Debt extinguishment2

311

5,434

3,715

Acquisition related

226

653

133

Change in FV convertible debt

(466)

1,273

(1,682)

Offering costs convertible debt

4,332

Other non-cash charges

(300)

Non-GAAP adjusted (loss)

(13,792)

(12,640)

(54,030)

(33,193)

Basic and Diluted shares outstanding

89,759

83,307

89,076

77,516

Non-GAAP adjusted (loss) income per share

($0.15)

($0.15)

($0.61)

($0.43)

1 Included in general and administrative expenses in the financial statements.

2 Included in other income and expenses.

Non-GAAP Operating Expenses

For the three months
ended December 31,

For the year ended
December 31,

2022

2021

2022

2021

Cost of revenue

1,618

441

3,614

585

Stock-based compensation expense

(7)

(16)

Net cost of revenue

1,611

441

3,598

585

Amortization of acquired intangible assets

506

123

1,784

146

Sales and marketing expense

5,759

3,340

19,318

8,895

Stock-based compensation expense

(605)

(363)

(2,464)

(1,177)

Net sales and marketing expense

5,154

2,977

16,854

7,718

General and administrative expense total

10,059

9,106

41,041

25,420

Depreciation and amortization expense

(920)

(75)

(673)

(80)

Stock-based compensation expense

(3,985)

(3,711)

(16,001)

(12,799)

Net general and administrative expense

5,154

5,320

24,367

12,541

Research and development expense total

6,674

6,969

25,547

19,847

Stock-based compensation expense

(352)

(306)

(1,051)

(1,033)

Net research and development expense

6,322

6,663

24,496

18,814

Total operating expenses

24,616

19,979

91,304

54,893

Depreciation and amortization

(1,426)

(198)

(2,457)

(226)

Stock-based compensation expense

(4,949)

(4,380)

(19,532)

(15,009)

Net Non-GAAP operating expenses

18,241

15,401

69,315

39,658

Ascentage Pharma to Present Latest Results from Three Preclinical Studies at 2023 American Association for Cancer Research Annual Meeting

On March 14, 2023 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that the latest results from three preclinical studies of the company’s novel third-generation BCR-ABL inhibitor olverembatinib (HQP1351) and two key assets of Ascentage Pharma’s apoptosis-targeting pipeline, the Bcl-2 inhibitor lisaftoclax (APG-2575) and the MDM2-p53 inhibitor alrizomadlin (APG-115), have been selected for presentations at the 2023 American Association of Cancer Research Annual Meeting (AACR 2023) (Press release, Ascentage Pharma, MAR 14, 2023, View Source [SID1234628708]). These results provide key findings that will support continued advances in the development of innovative therapeutics. Abstracts featuring these results have already been published in the AACR (Free AACR Whitepaper)’s official website.

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The AACR (Free AACR Whitepaper) annual meeting is one of the world’s largest and longest-standing scientific gatherings in the field of cancer research. Covering some of the most cutting-edge advances in all the areas of oncology research and innovation, the annual event attracts tremendous interest from the global cancer research community. This year’s AACR (Free AACR Whitepaper) annual meeting will be held from April 14-19, 2023, in Orlando, Florida, USA.

These three abstracts from Ascentage Pharma include:

Olverembatinib (HQP1351)
Olverembatinib (HQP1351) enhances antitumor effects of immunotherapy in renal cell carcinoma (RCC)

Abstract#: 5071
Track: Immunology
Session Title: Combination Immunotherapies 1
Session Time: Tuesday, April 18, 2023, 1:30 PM-5:00 PM, EDT
Our results suggest that combining olverembatinib with a checkpoint inhibitor (CPI) confers synergistic antitumor effects in an RCC cancer mouse model by targeting tumor growth, angiogenesis, and immune regulation. This novel combination may provide an alternative approach to enhance treatment effects with CPIs in renal cancers.

Olverembatinib (HQP1351) plus Lisaftoclax (APG-2575)
Combination of olverembatinib (HQP1351) with BCL-2 inhibitor lisaftoclax (APG-2575) overcomes resistance in gastrointestinal stromal tumors (GISTs)

Abstract#: 1631
Track: Experimental and Molecular Therapeutics
Session Title: Novel Antitumor Agents 3
Session Time: Monday, April 17, 2023, 9:00 AM-12:30 PM, EDT
Our results demonstrate that olverembatinib and Bcl-2 inhibitor lisaftoclax have synergistic antitumor effects in imatinib-resistant GIST. Considering that the resistance mechanisms are similar for most tyrosine kinase inhibitors (TKIs), this novel dual approach may have the potential for treating patients with GISTs whose disease has progressed after treatment with imatinib or other TKIs.

Alrizomadlin (APG-115)
MDM2 inhibitor alrizomadlin (APG-115) promotes antitumor activity of mitogen-activated protein kinase (MAPK) inhibitors in uveal melanoma

Abstract#: 1632
Track: Experimental and Molecular Therapeutics
Session Title: Novel Antitumor Agents 3
Session Time: Monday, April 17, 2023, 9:00 AM-12:30 PM, EDT
Our results demonstrate the potential utility of combining alrizomadlin with MAPK pathway inhibitors to treat patients with uveal melanoma.

Miravo Healthcare™ and Searchlight Pharma Inc. Announce Closing of Arrangement

On March 14, 2023 Nuvo Pharmaceuticals Inc. d/b/a Miravo Healthcare (TSX:MRV; OTCQX:MRVFF) ("Miravo" or the "Company") and Searchlight Pharma Inc., a private Canadian-based specialty healthcare company ("Searchlight"), reported the closing of the previously reported plan of arrangement (the "Arrangement") of Miravo with Searchlight (Press release, Nuvo Pharmaceuticals, MAR 14, 2023, View Source [SID1234628654]). Under the terms of Arrangement, Searchlight acquired all the issued and outstanding common shares of the Company (the "Company Shares") in exchange for cash consideration of $1.35 per Company Share.

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"Today marks the beginning of a new chapter for Miravo as it officially combines with Searchlight and continues as a private company," said Mark Nawacki, President and CEO of Searchlight Pharma Inc. "Searchlight plus Miravo will be a diversified, large and strong company – based on IQVIA CDH sales data, we will rank in the top three of Canadian specialty pharma companies – and this positions us well to continue to execute our successful business model and to deliver on our leadership objective in the sector. On behalf of the Searchlight team, I express our thanks to all Miravo stakeholders for their cooperation throughout this acquisition process, and I warmly welcome our new Miravo colleagues to the Searchlight family."

The Company Shares will be de-listed from the TSX and the Company will apply to cease to be a reporting issuer in each of the provinces of Canada.

Registered shareholders of the Company are reminded that they must properly complete, sign and return the letter of transmittal, along with their share certificate(s), to TSX Trust Company, as depositary, in order to receive the consideration they are entitled to under the Arrangement. Non-registered shareholders of the Company will receive the consideration they are entitled to under the Arrangement through the intermediary in whose name their Company Shares are registered.

If any shareholder of the Company has questions with respect to the letter of transmittal, please contact the Depositary, toll free at 1-800-387-0825, or by email at [email protected].

Early Warning Disclosure

Prior to the Arrangement, Searchlight owned no Company Shares. In connection with the Arrangement, Searchlight acquired 11,388,282 Company Shares, representing 100% of the issued and outstanding Company Shares, for cash consideration of $1.35 per Company Share. A copy of the related early warning report will be available under the Company’s SEDAR profile at www.sedar.com and may be obtained from Searchlight upon request by phone at (514) 613-1513 or by email at [email protected]. Searchlight’s head office is located at 1600 Notre-Dame Street West, Suite 312, Montréal, Québec, H3J 1M1.

HotSpot Therapeutics to Present Two Poster Presentations on CBL-B Program at AACR Annual Meeting 2023

On March 14, 2023 HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies targeting regulatory sites on proteins referred to as "natural hotspots," reported it will present two poster presentations on the company’s CBL-B program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, taking place April 14-19, 2023, in Orlando, FL (Press release, Ascentage Pharma, MAR 14, 2023, View Source [SID1234628707]). One poster will describe preclinical data for the CBL-B program, and one Clinical Trials in Progress poster will describe the first-in-human Phase 1/2 clinical trial of HST-1011.

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Presentation details are as follows:

Title: Inhibition of the E3 ligase CBL-B enhances the effector function and proliferation of natural killer cells
Session Title: Late-Breaking Research: Immunology 3
Session Date and Time: Wed., Apr. 19, 9:00 AM-12:30 PM ET
Location: Poster Section 36
Poster Board Number: 5
Abstract Number: LB337

Title: Phase 1/2 study of HST-1011, an oral CBL-B inhibitor, alone and in combination with anti-PD1 in patients with advanced solid tumors
Session Title: Phase I and First-in-Human Clinical Trials in Progress
Session Date and Time: Tue., Apr. 18, 1:30-5:00 PM ET
Location: Poster Section 46
Poster Board Number: 14
Abstract Number: CT251

About HST-1011
HST-1011 is an investigational orally bioavailable, selective, small molecule allosteric inhibitor of CBL-B, an E3 ubiquitin protein ligase critically involved in immune cell response. Because CBL-B functions as a master regulator of effector cell (T cell and natural killer cell) immunity, its inactivation removes its endogenous negative regulatory functions to substantially enhance anti-tumor immunity. Preclinical data has demonstrated HST-1011’s ability to bind to and inhibit a natural hotspot on CBL-B, yielding the activation and propagation of a targeted anti-tumor immune response. Enabled by HotSpot’s proprietary Smart AllosteryTM platform, HST-1011 is designed with tight binding, low nanomolar potency, a slow dissociation rate from the target to enable sustained pharmacology, and greater selectivity for CBL-B relative to C-CBL.