On October 31, 2024 Evaxion Biotech A/S (NASDAQ: EVAX) ("Evaxion"), a clinical-stage TechBio company specializing in developing AI-Immunology powered vaccines, reported business update and provided third quarter 2024 financial results (Press release, Evaxion Biotech, OCT 31, 2024, View Source [SID1234647600]).

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Business highlights (since last quarterly update)

Since the second quarter 2024 business update, we have continued to execute strongly on our strategy and plans with several major milestones achieved. Key highlights include:

Significant expansion of the infectious disease vaccine development collaboration with MSD (tradename of Merck & co., Inc., Rahway, NJ, USA) in a transformative deal for Evaxion
Continuously increasing external interest and several ongoing partnerships discussions covering both our platform and pipeline
Strong progress in clinical and preclinical development with convincing phase 2 data presented for personalized cancer vaccine EVX-01 and preclinical Proof-of-Concept obtained for EVX-B2 mRNA Gonorrhea vaccine candidate
Launch of improved AI-Immunology platform for vaccine antigen prediction
Thomas Schmidt appointed as interim Chief Financial Officer
"We continued to make solid progress on our strategy execution in a busy third quarter and are very pleased to have achieved several important milestones across our company. The MSD agreement, which holds the potential to transform Evaxion over the coming years, and the groundbreaking EVX-01 phase 2 efficacy data, stand out among our many achievements. We continue to demonstrate our strong capabilities as a truly AI-based TechBio company and remain focused on advancing on-going partnerships as well as new partnership discussions, progressing the EVX-01 trial and carrying through preclinical studies as a basis for expanding our R&D pipeline," says Christian Kanstrup, CEO of Evaxion.

2024 Milestones

Milestones Target
EVX-B1 Conclusion of final MTA study with potential partner Q1 2024 ✓
AI-Immunology Launch of EDEN model version 5.0 Mid 2024
(ECCB, September) ✓
EVX-B2-mRNA EVX-B2-mRNA preclinical Proof-of-Concept obtained Q3 2024
(18th Vaccine Congress, September) ✓
EVX-01 Phase 2 one-year readout Q3 2024
(ESMO Congress, September) ✓
EVX-B3 Conclusion of target discovery and validation work in collaboration with MSD (tradename of Merck & Co., Inc., Rahway, NJ, USA)* H2 2024 (✓)
Precision ERV cancer vaccines Preclinical Proof-of-Concept obtained H2 2024
Funding Ambition for full year 2024 is to generate business development income or cash in equal to 2024 cash burn (excluding financing activities) of $14 million**
* MSD option and license agreement on EVX-B2 and EVX-B3 supersedes this milestone
** See update on the business development income ambition below

Research & Development update

We maintain a high activity level in Research & Development (R&D) from both a preclinical and clinical perspective. This work yielded outstanding results in the third quarter, first and foremost with the presentation of encouraging one-year data from the ongoing phase 2 trial with our lead asset EVX-01, an AI-Immunology designed personalized cancer vaccine, in patients with advanced melanoma (skin cancer).

The data demonstrates 69% Overall Response Rate, reduction in tumor target lesions in 15 out of 16 patients, an immunogenicity rate of 79%, and a positive correlation between our AI-Immunology platform predictions and immune responses induced by the individual neoantigens in the EVX-01 vaccine (p=0.00013). The observed immunogenicity rate means that 79% of EVX-01’s vaccine targets triggered a targeted immune response, which compares very favorably to what is seen with other approaches.

These clinical findings underscore the significant therapeutic potential of EVX-01 and are yet another validation of the AI-Immunology platform as a leading AI technology for fast and effective vaccine target discovery and design.

We were also successful in our preclinical research, obtaining Proof-of-Concept for novel mRNA Gonorrhea vaccine candidate EVX-B2. This was based on new data documenting that EVX-B2 mRNA triggers a targeted immune response that leads to the elimination of the gonorrhea bacteria. The same had earlier been shown for the protein-based version of EVX-B2, which is now part of our partnership with MSD. The mRNA data has been generated as part of our partnership with Afrigen Biologics.

Further to our pipeline, our R&D investments are also allocated to the continued improvement of our AI-Immunology platform. During the third quarter, we updated the platform with the launch of a new version of its EDEN AI prediction model. Among other improvements, the model can now predict toxin antigens, allowing for the development of improved bacterial vaccines. We expect this update to further solidify the strong interest seen in AI-Immunology from potential partners.

Business development income

Our strategy is based upon a multi-partner approach, making effective execution upon our business development plans crucial to our success. We were thrilled to sign the significantly expanded vaccine development collaboration with MSD during the third quarter. Further, we continue to see an increasing interest from potential partners and are excited by the current partnership opportunities both around existing pipeline assets as well as our AI-Immunology platform.

The agreement with MSD carries potential business development income of up to $10 million for 2025 on top of the $3.2 million upfront payment received in 2024. Based upon the current business development opportunities, we remain confident in our ability to execute upon our multi-partner strategy and bring in significant business development income.

Given that certain partnership discussions will be moving into 2025, we will – despite the strong interest – not be able to meet our 2024 ambition of generating business development income or cash in of $14 million. The discussions, having moved into 2025, will however support the generation of business development income for next year in addition to the potential up to $10 million from MSD.

Nasdaq dialogue

As communicated earlier, on May 7, 2024, we received a deficiency letter from Nasdaq Stock Market LLC ("Nasdaq") for failure to maintain stockholders’ equity of at least $2.5 million, following which we presented a plan to Nasdaq to regain compliance. Nasdaq provided us until November 4, 2024, to evidence compliance based upon the plan submitted.

We remain committed to ensuring compliance with the Nasdaq minimum stockholder’s equity requirement and maintain our Nasdaq listing. This is to be pursued through increasing shareholder’s equity via a combination of business development income and capital markets activities. However, current equity market environment, the geopolitical uncertainties and timing of business development activities have to date impacted timing for the full required increase in shareholder’s equity.

We do not expect to have regained compliance by November 4, 2024, and therefore expect Nasdaq to send us a delisting notification after such date. We then plan to appeal the delisting determination and request a hearing on the matter, following which a new 180-day extension could be granted based on our plan to regain compliance.

We are in constructive dialogue with Nasdaq around this process, though we will not receive any guarantee that another 180-day extension will be granted before the anticipated hearing.

Third quarter 2024 financial results

Cash position as of September 30, 2024, was $4.6 million, as compared to $5.6 million as of December 31, 2023. The cash position as of September 30, excludes the $3.2 million upfront from the MSD agreement which was received in October. The Company expects that its existing cash and cash equivalents will be sufficient to fund its operating expenses and capital expenditure requirements into March 2025.

Revenue of $3.0 million was recognized for the quarter ending September 30, 2024, as compared to nil for the quarter ending September 30, 2023. A minor proportion of this revenue derives from the existing EVX-B3 collaboration with MSD, while the majority relates to the newly signed option and license agreement with MSD.

Research and Development expenses were $2.6 million for the quarter ending September 30, 2024, as compared to $2.8 million for the quarter ending September 30, 2023. The decrease is primarily related to a reduced headcount.

General and Administrative expenses were $2.1 million for the quarter ending September 30, 2024, as compared to $2.9 million for the quarter ending September 30, 2023. The decrease was primarily due to a decrease in expenses to management remuneration following changes to executive management in 2023 and expenses related to this. In addition, various minor cost reductions related to overhead and professional fees are realized.

We generated a net loss of $1.9 million for the quarter ending September 30, 2024, or $(0.04) per basic and diluted share, as compared to a net loss of $5.7 million, or $(0.21) per basic and diluted share for the quarter ending September 30, 2023. The decreased loss was primarily driven by the recognized revenue and reduced general & administrative expenses.

Total equity amounts to $0.1 million as of September 30, 2024. Proceeds from the exercise of prefunded warrants amounted to $0.2 million for the quarter.

Evaxion Biotech A/S
Consolidated Statement of Financial Position Data (Unaudited)
(USD in thousands)

Sep 30,
2024 Dec 31,
2023
Cash and cash equivalents 4,576 5,583
Total assets 15,185 12,889
Total liabilities 15,111 17,618
Share capital 8,732 5,899
Other reserves 106,245 99,946
Accumulated deficit (114,903) (107,860)
Total equity before derivative warrant liability 74 (2,015)
Effect from derivative liabilities from investor warrants - (2,714)
Total equity 74 (4,729)
Total liabilities and equity 15,185 12,889

Based on the Company’s current cash position with an expected cash runway into March 2025, income from Business Development deals and/or further funding is required to mitigate the conclusion that there is significant doubt about the Company’s ability to continue as a going concern. Please refer to the Form 20-F, filed March 27, 2024, for additional background on the Company.

Evaxion Biotech A/S
Consolidated Statement of Comprehensive Loss Data (Unaudited)
(USD in thousands, except per share data)

Three Months Ended
September 30, Nine Months Ended
September 30,
2024 2023 2024 2023
Revenue 3,017 — 3,222 —
Research and development (2,614) (2,830) (8,202) (9,618)
General and administrative (2,134) (2,932) (5,728) (8,215)
Operating loss (1,731) (5,762) (10,708) (17,833)
Finance income 84 72 5,922 404
Finance expenses (384) (182) (2,665) (786)
Net loss before tax (2,031) (5,872) (7,451) (18,215)
Income tax benefit 96 194 513 613
Net loss for the period (1,935) (5,678) (6,938) (18,215)
Net loss attributable to shareholders of Evaxion Biotech A/S (1,935) (5,678) (6,938) (18,215)
Loss per share – basic and diluted (0.04) (0.21) (0.13) (0.66)
Number of shares used for calculation (basic and diluted) 55,255,329 27,659,878 51,905,948 26,754,440

On October 31, 2024 Cidara Therapeutics, Inc. (Nasdaq: CDTX), a biotechnology company using its proprietary Cloudbreak platform to develop drug-Fc conjugate (DFC) immunotherapies designed to save lives and improve the standard of care for patients facing serious diseases, reported that Jeffrey Stein, Ph.D., President and Chief Executive Officer, will participate in the following November investor conferences (Press release, Cidara Therapeutics, OCT 31, 2024, View Source [SID1234647599]).

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Details are as follows:

Event: Guggenheim Securities Healthcare Innovation Conference
Date: Monday, November 11, 2024
Time: 1:30 PM ET
Format: Fire side chat
Webcast: View Source

A replay of the presentation will be available in the Investors section on the Company’s website at www.cidara.com. The replay of the presentation will be available for 90 days.

Event: Jefferies London Healthcare Conference
Date: Tuesday, November 19 – Thursday, November 21, 2024

Cidara will participate in one-on-one investor meetings during these events. Investors interested in meeting with Cidara at the conferences should contact the appropriate conference directly.

On October 31, 2024 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science, reported financial results for the third quarter ended September 30, 2024, as well as recent business highlights (Press release, C4 Therapeutics, OCT 31, 2024, View Source [SID1234647584]).

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"2024 has been a successful year for C4T marked by strong execution across our entire portfolio, which has continued to position us as a leader in targeted protein degradation science. We recently shared initial clinical data on CFT1946 demonstrating a well-tolerated safety profile and evidence of monotherapy anti-tumor activity in BRAF inhibitor exposed patients, and we delivered our second development candidate to Biogen," said Andrew Hirsch, president and chief executive officer of C4 Therapeutics. "We look forward to continuing this momentum with cemsidomide Phase 1 data in multiple myeloma and in non-Hodgkin’s lymphoma being presented at ASH (Free ASH Whitepaper), and multiple CFT1946 data readouts expected in 2025. Our continued focus on discovery research, clinical development and collaborations sets us up for an exciting future and for the potential to improve patients’ lives."

THIRD QUARTER 2024 AND RECENT ACHIEVEMENTS

Cemsidomide: Cemsidomide is an oral degrader of IKZF1/3 for the potential treatment of relapsed/refractory (R/R) multiple myeloma (MM) and R/R non-Hodgkin’s lymphoma (NHL).
•Advanced the Phase 1/2 Clinical Trial. The cemsidomide Phase 1/2 trial in combination with dexamethasone for R/R MM and as a monotherapy for R/R NHL continues to enroll patients. Dose escalation continues as the maximum tolerated dose has not yet been reached. For the combination with dexamethasone MM arm, patients are now enrolling at dose level 6 (100 µg once daily (QD)) and enrollment in the dose level 5 (75 µg QD) expansion cohort is complete. The monotherapy NHL arm continues to progress and dose level 5 (100 µg QD) is the highest dose level evaluated to date.
CFT1946: CFT1946 is an oral degrader targeting BRAF V600 mutations for the potential treatment of solid tumors including colorectal cancer (CRC), melanoma and non-small cell lung cancer (NSCLC).
•Presented New Preclinical Data at the 7th Annual Targeted Protein Degradation (TPD) Summit: In October 2024, C4T shared new in vivo data for CFT1946 describing Kpu,u (range: 0.34 – 0.88), experimentally determined using independent methods in two different species. These results demonstrate CFT1946’s ability to cross the blood brain barrier and highlight the potential for activity in primary and metastatic central nervous system (CNS) disease.
•Presented Monotherapy Clinical Data Demonstrating Proof of Mechanism and Early Evidence of Proof of Concept from the Ongoing CFT1946 Phase 1 Trial at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024: CFT1946 demonstrated a well-tolerated safety profile and evidence of monotherapy anti-tumor activity, which supports further clinical development as monotherapy and in combination with MEK and EGFR targeted therapies.
•Advanced the Phase 1/2 Clinical Trial. The CFT1946 Phase 1/2 trial for BRAF V600 mutant solid tumors continues to enroll patients across multiple arms of the trial:
◦CFT1946 Monotherapy Dose Escalation in BRAF V600 Mutant Solid Tumors: Patients continue to enroll in the 640 mg twice daily (BID) pharmacodynamic (PD) backfill cohort.
◦CFT1946 Monotherapy Melanoma Expansion Cohorts: Enrollment at the 320 mg BID dose level is complete and patients are enrolling at the 640 mg BID dose level.
◦CFT1946 with Cetuximab Phase 1b Dose Escalation for CRC: The 160 mg BID dose level has been declared safe and patients are enrolling at the 320 mg BID dose level.
RESEARCH UPDATES:
•Presented at the 7th Annual TPD Summit Highlighting C4T’s TORPEDO Platform: In October 2024, at the 7th Annual TPD Summit, C4T presented kinetics-based pharmacokinetic (PK) and PD models, demonstrating the company’s ability to predict clinical PD responses across target classes.
COLLABORATIONS:
•Delivered Second Development Candidate to Biogen. In September 2024, C4T earned an additional $8 million milestone payment after Biogen accepted delivery of a second development candidate in an undisclosed indication. Biogen is responsible for all future clinical development and commercialization for this program. This marks the final development candidate under this strategic collaboration.
CORPORATE UPDATES:
•In October 2024, C4T appointed Paige Mahaney, Ph.D., as the company’s chief scientific officer, succeeding Stew Fisher, Ph.D., who is retiring to pursue personal interests. Dr. Mahaney brings over 25 years of pharmaceutical executive leadership with multidisciplinary expertise in discovery research and development along with successfully building clinical portfolios across a wide range of disease indications and treatment modalities.
•In September 2024, C4T appointed Stephen Fawell, Ph.D., to the Board of Directors. Dr. Fawell brings decades of experience leading discovery and development strategies for global pharmaceutical companies.
KEY UPCOMING MILESTONES
Cemsidomide:

•Present updated dose escalation and expansion cohort data from the 50 µg M/W/F, 37.5 µg QD, 62.5 µg QD, and 75 µg QD dose levels in approximately 40 patients from the ongoing Phase 1/2 clinical trial with dexamethasone in R/R MM at the ASH (Free ASH Whitepaper) Annual Meeting in December 2024.
•Present dose escalation data from the 25 µg M/W/F, 50 µg M/W/F, 37.5 µg QD, 62.5 µg QD, and 100 µg QD dose levels in approximately 25 patients from the ongoing monotherapy Phase 1/2 clinical trial in R/R NHL at the ASH (Free ASH Whitepaper) Annual Meeting in December 2024.
•Complete Phase 1 dose exploration in R/R MM and R/R NHL by year-end.
CFT1946:
•Initiate the Phase 1b dose escalation cohort evaluating CFT1946 in combination with trametinib in melanoma by year-end.
•Present data from multiple anticipated readouts in 2025, including:
◦Full monotherapy CFT1946 dose escalation cohorts in BRAF V600 mutant solid tumors.
◦Expansion cohorts evaluating CFT1946 as a monotherapy in melanoma.
◦Phase 1b dose escalation cohort evaluating CFT1946 in combination with cetuximab in CRC.
UPCOMING INVESTOR EVENTS:
•November 20, 2024, at 8 am GT: Management will participate in a fireside chat at the Jefferies London Healthcare conference taking place in London, UK.
•December 8, 2024: Management will host an investor call to discuss MM and NHL data from the ongoing Phase 1/2 trial of cemsidomide.
THIRD QUARTER 2024 FINANCIAL RESULTS
Revenue: Total revenue for the third quarter of 2024 was $15.4 million, compared to $11.1 million for the third quarter of 2023. The increase in revenue was primarily due to recognition of an $8.0 million milestone from Biogen as well as $2.9 million of revenue recognized under our license and supply agreement with Betta, partially offset by reduced revenue from our agreement with Roche due to the completion of research activities in the third quarter of 2023 for a nominated target. Total revenue for the third quarter of 2024 reflects revenue recognized under our collaborations with Biogen, Betta, Merck, Merck KGaA, Darmstadt, Germany (MKDG) and Roche, and total revenue recognized in the third quarter of 2023 reflects revenue recognized under collaboration agreements with Biogen and Roche.
Research and Development (R&D) Expense: R&D expense for the third quarter of 2024 was $31.8 million, compared to $28.3 million for the third quarter of 2023. The increase in R&D expense was primarily due to increased clinical trial expense as cemsidomide and CFT1946 continue to advance, partially offset by lower personnel costs.
General and Administrative (G&A) Expense: G&A expense was $11.8 million for the third quarter of 2024, compared to $10.5 million for the third quarter of 2023. The increase in G&A expense was primarily attributable to higher personnel expense related to stock-based compensation.
Net Loss and Net Loss per Share: Net loss for the third quarter of 2024 was $24.7 million, compared to $27.0 million for the third quarter of 2023. Net loss per share for the third quarter of 2024 was $0.35 compared to $0.55 for the third quarter of 2023.
Cash Position and Financial Guidance: Cash, cash equivalents and marketable securities as of September 30, 2024 were $284.4 million, compared to $295.7 million as of June 30, 2024, and $281.7 million as of December 31, 2023. The reduction in cash, cash equivalents and marketable securities during the third quarter was primarily the result of cash used in operating activities, partially offset by $10.3 million in net proceeds raised through our at-the-market (ATM) facility. C4T expects that its cash, cash equivalents and marketable securities as of September 30, 2024 will be sufficient to fund planned operating expenses and capital expenditures into 2027.

On October 31, 2024 Bristol Myers Squibb (NYSE: BMY) reported results for the third quarter of 2024 (Press release, Bristol-Myers Squibb, OCT 31, 2024, View Source [SID1234647583]).

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"We made important strides in the third quarter with the landmark U.S. approval of Cobenfy in schizophrenia, continued sales momentum, strong cash flow generation and key pipeline achievements," said Christopher Boerner, Ph.D., board chair and chief executive officer, Bristol Myers Squibb. "We’re focused on closing out the year with strong execution as we deliver on our Growth Portfolio, prioritize high-growth opportunities and continue delivering transformational results for patients."

Third Quarter

$ in millions, except per share amounts

2024

2023

Change

Change Excl.
F/X**

Total Revenues

$11,892

$10,966

8%

10%

Earnings Per Share — GAAP*

0.60

0.93

(35)%

N/A

Earnings Per Share — Non-GAAP* **

1.80

2.00

(10)%

N/A

Acquired IPRD Charge and Licensing Income Net Impact on Earnings Per Share

(0.09

)

(0.03

)

N/A

N/A

*GAAP and Non-GAAP earnings per share include the net impact of Acquired IPRD charges and licensing income.

**See "Use of Non-GAAP Financial Information".

THIRD QUARTER RESULTS
All comparisons are made versus the same period in 2023 unless otherwise stated.

Bristol Myers Squibb posted third quarter revenues of $11.9 billion, an increase of 8%, or 10% when adjusted for foreign exchange impacts, primarily driven by the Growth Portfolio and Eliquis, partially offset by generic erosion of Sprycel due to the loss of exclusivity.
U.S. revenues increased 9% to $8.2 billion, and International revenues increased 7% to $3.7 billion, primarily due to the Growth Portfolio and higher demand for Eliquis, partially offset by generic erosion of Sprycel due to the loss of exclusivity. The negative impact from foreign exchange on International revenues was 4%.
On a GAAP basis, gross margin decreased from 77.1% to 75.1%, and on a non-GAAP basis decreased from 77.3% to 76.0%, primarily due to product mix.
On a GAAP and non-GAAP basis, marketing, selling and administrative expenses remained relatively flat at $2.0 billion.
On a GAAP basis, research and development expenses increased 6%, and 8% on a non-GAAP basis, to $2.4 billion, primarily due to recent acquisitions.
On a GAAP and non-GAAP basis, Acquired IPRD increased to $262 million from $80 million. On a GAAP and non-GAAP basis, licensing income was $25 million compared to $12 million.
On a GAAP basis, amortization of acquired intangible assets increased 7% to $2.4 billion, primarily due to the RayzeBio acquisition in 2024 and approval of Augtyro in the fourth quarter of 2023.
On a GAAP basis, the effective tax rate increased from 9.5% to 27.5%, and on a non-GAAP basis increased from 11.6% to 18.5%, primarily due to jurisdictional earnings mix and adjustments in 2023 to reflect IRS income tax guidance issued in 2023 regarding deductibility of certain non-U.S. research and development expenses.
On a GAAP basis, the company reported net income attributable to Bristol Myers Squibb of $1.2 billion, or $0.60 per share, during the third quarter of 2024 compared to $1.9 billion, or $0.93 per share, for the same period a year ago. The company reported non-GAAP net earnings attributable to Bristol Myers Squibb of $3.7 billion, or $1.80 per share, during the third quarter of 2024 compared to $4.1 billion, or $2.00 per share, for the same period a year ago. In addition to the items above, GAAP and non-GAAP earnings per share were impacted by higher interest expense.

THIRD QUARTER PRODUCT REVENUE HIGHLIGHTS

($ amounts in millions)

Quarter Ended September
30, 2024

% Change from Quarter
Ended September 30,
2023

% Change from
Quarter Ended
September 30,
2023 Ex-F/X**

U.S.

Int’l (c)

WW (d)

U.S.

Int’l (c)

WW (d)

Int’l (c)

WW (d)

Growth Portfolio

Opdivo

$

1,366

$

994

$

2,360

2%

7%

4%

16%

7%

Orencia

706

230

936

—%

6%

1%

13%

3%

Yervoy

399

243

642

11%

10%

11%

17%

13%

Reblozyl

358

89

447

79%

85%

80%

90%

81%

Opdualag

216

17

233

33%

>200%

40%

>200%

40%

Abecma

77

47

124

12%

96%

33%

100%

34%

Zeposia

105

42

147

11%

50%

20%

46%

19%

Breyanzi

173

51

224

125%

>200%

143%

>200%

143%

Camzyos

135

21

156

101%

>200%

129%

>200%

129%

Sotyktu

51

15

66

(18)%

>200%

—%

>200%

—%

Augtyro

10

—

10

N/A

N/A

N/A

N/A

N/A

Krazati

32

2

34

N/A

N/A

N/A

N/A

N/A

Other Growth Products (a)

172

261

433

15%

61%

39%

64%

41%

Total Growth Portfolio

3,800

2,012

5,812

15%

22%

18%

29%

20%

Legacy Portfolio

Eliquis

2,045

957

3,002

15%

3%

11%

2%

11%

Revlimid

1,212

200

1,412

—%

(9)%

(1)%

(6)%

(1)%

Pomalyst/Imnovid

697

201

898

15%

(24)%

3%

(24)%

3%

Sprycel

225

65

290

(44)%

(45)%

(44)%

(42)%

(43)%

Abraxane

151

102

253

(15)%

24%

(3)%

37%

1%

Other Legacy Products (b)

102

123

225

17%

(18)%

(5)%

(19)%

(5)%

Total Legacy Portfolio

4,432

1,648

6,080

4%

(7)%

1%

(6)%

1%

Total Revenues

$

8,232

$

3,660

$

11,892

9%

7%

8%

11%

10%

**

See "Use of Non-GAAP Financial Information".

(a)

Includes Nulojix, Onureg, Inrebic, Empliciti and royalty revenue.

(b)

Includes other mature brands.

(c)

Beginning in 2024, Puerto Rico revenues are included in International revenues. Prior period amounts have been reclassified to conform to the current presentation.

(d)

Worldwide (WW) includes U.S. and International (Int’l).

THIRD QUARTER PRODUCT REVENUE HIGHLIGHTS
Growth Portfolio
Growth Portfolio worldwide revenues increased to $5.8 billion compared to $4.9 billion in the prior year period, representing growth of 18% on a reported basis or 20% when adjusted for foreign exchange impacts. Growth Portfolio revenues were primarily driven by higher demand for Reblozyl, Breyanzi, Camzyos and Opdualag.

Legacy Portfolio
Revenues for the Legacy Portfolio in the third quarter were $6.1 billion compared to $6.0 billion in the prior year period, representing growth of 1% on a reported basis and when adjusted for foreign exchange impacts. Legacy Portfolio revenues were primarily driven by higher demand for Eliquis , partially offset by a decline in demand for Sprycel due to generic erosion.

PRODUCT AND PIPELINE UPDATE
Bristol Myers Squibb recently achieved several important clinical and regulatory milestones, including the U.S. approval of Cobenfy and the disclosure of long-term cardiovascular and oncology data that underscore the strength of the company’s science.

With Cobenfy, the company is re-establishing its presence in neuroscience and introducing the first new pharmacological approach to treat schizophrenia in decades.

Today, the company is providing an update on data from two Phase 3 oncology trials, CheckMate -8HW and CheckMate -901. Please see the table below for more information.

Neuroscience

Category

Asset

Milestone

Regulatory

Cobenfy TM
(xanomeline and
trospium
chloride)

The U.S. Food and Drug Administration (FDA) approved Cobenfy, previously referred to as KarXT, for the treatment of schizophrenia in adults, with a mechanism of action distinct from current therapies. The approval is based on data from the EMERGENT clinical program, which includes three placebo-controlled efficacy and safety trials and two open-label trials evaluating the long-term safety and tolerability of Cobenfy for up to one year.

Cardiovascular

Category

Asset

Milestone

Clinical &
Research

Camzyos
(mavacamten)

Long-term follow-up results from the EXPLORER-LTE cohort of the MAVA-Long-Term Extension study evaluating Camzyos in adult patients with New York Heart Association (NYHA) class II-III symptomatic obstructive hypertrophic cardiomyopathy demonstrated that patients experienced consistent and sustained improvements in echocardiographic measures and biomarkers after up to 3.5 years of continuous treatment.

Patients experienced an improvement in symptoms and functional capacity as measured by NYHA class and patient-reported outcomes. The safety profile of Camzyos for up to 3.5 years remained consistent with the established safety profile and no new safety signals were identified.

Oncology

Category

Asset

Milestone

Regulatory

Opdivo
(nivolumab)

The FDA approved Opdivo for the treatment of adult patients with resectable (tumors ≥ 4cm or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements, for neoadjuvant treatment, in combination with platinum-doublet chemotherapy, followed by single-agent Opdivo as adjuvant treatment after surgery. The approval is based on results from the Phase 3 randomized CheckMate -77T trial.

Opdivo +
Yervoy
(ipilimumab)

The FDA accepted the supplemental Biologics License Application for Opdivo plus Yervoy as a potential first-line treatment for adult patients with unresectable hepatocellular carcinoma. The acceptance is based on results from the Phase 3 CheckMate -9DW trial. The FDA assigned a Prescription Drug User Fee Act goal date of April 21, 2025.

Clinical &
Research

Opdivo

The Phase 3 CheckMate -8HW trial evaluating Opdivo plus Yervoy compared to Opdivo monotherapy across all lines of therapy as a treatment for patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer met the dual primary endpoint of progression-free survival (PFS) as assessed by Blinded Independent Central Review at a pre-specified interim analysis. Previously, Opdivo plus Yervoy demonstrated a statistically significant and clinically meaningful improvement in PFS compared to chemotherapy.

Opdivo plus Yervoy demonstrated a statistically significant and clinically meaningful improvement in PFS compared to Opdivo monotherapy across all lines of therapy. The study is ongoing to assess various secondary endpoints, including overall survival (OS). The safety profile for the combination of Opdivo plus Yervoy remained consistent with previously reported data, with no new safety signals identified.

Opdivo

The Phase 3 CheckMate -901 trial evaluating Opdivo plus Yervoy versus standard-of-care non-cisplatin-based chemotherapy in patients with unresectable or metastatic urothelial carcinoma (UC) who are ineligible for cisplatin-based chemotherapy did not meet its primary endpoint of OS. The safety profile for Opdivo and Yervoy was consistent with previously reported data, with no new safety signals identified.

Opdivo has previously shown clinical benefit across various stages of UC. These results do not impact those data or approved indications.

nivolumab +
relatlimab high
dose

The company announced plans to initiate a Phase 3 trial evaluating the fixed-dose combination of nivolumab and high-dose relatlimab plus chemotherapy as a first-line treatment for stage IV or recurrent non-squamous NSCLC with tumor cell PD-L1 expression of 1 to 49%. The decision was supported by findings from the Phase 2 RELATIVITY-104 trial.

Opdivo +
Yervoy

10-year follow-up data from the Phase 3 CheckMate -067 trial showed continued durable improvement in survival with first-line Opdivo plus Yervoy therapy and Opdivo monotherapy, versus Yervoy alone, in patients with previously untreated advanced or metastatic melanoma. With a minimum follow up of 10 years, median OS was 71.9 months with Opdivo plus Yervoy, the longest reported median OS in a Phase 3 advanced melanoma trial.

Hematology

Category

Asset

Milestone

Regulatory

Breyanzi
(lisocabtagene
maraleucel)

The European Medicines Agency (EMA) validated the Type II variation application to expand the indication for Breyanzi to include the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received two or more prior lines of systemic therapy. The application is supported by data from the Phase 2 TRANSCEND FL study. Validation of the application confirms the submission is complete and begins the EMA’s centralized review process.

In addition, Japan’s Ministry of Health, Labour and Welfare approved the supplemental New Drug Application for Breyanzi for the treatment of relapsed or refractory FL after one prior line of systemic therapy in patients with high-risk FL and after two or more lines of systemic therapy.

Immunology

Category

Asset

Milestone

Clinical &
Research

Zeposia
(ozanimod)

Data from the Phase 3 DAYBREAK trial demonstrated that decreased rates of brain volume loss were sustained in the open-label extension (OLE) for patients treated with Zeposia for relapsing forms of multiple sclerosis.

A separate DAYBREAK OLE safety analysis demonstrated declining or stable incidence rates of treatment-emergent adverse events, with relatively low rates of infections, serious infections and opportunistic infections over more than eight years of treatment with Zeposia .

Financial Guidance
Bristol Myers Squibb is raising its 2024 line-item guidance as noted below.

2024 Line-Item Guidance

Non-GAAP 2

July
(Prior)

October
(Updated)

Total Revenues

Upper end of low single-
digit range

~5% increase

Total Revenues
(excl. F/X)

Upper end of low single-
digit range

~6% increase

Gross Margin %

Between ~74% and ~75%

Between ~74.5% and ~75%

Operating Expenses 1

Low single-digit increase

~4% to ~5% increase

Other income/(expense)

~($50M)

~$125M

Effective tax rate

~66%

~60%

Diluted EPS

$0.60 – $0.90

$0.75 – $0.95

1 Operating Expenses = MS&A and R&D, excluding Acquired IPRD and Amortization of acquired intangible assets.

2 See "Use of Non-GAAP Financial Information."

The 2024 financial guidance excludes the impact of any potential future strategic acquisitions, divestitures, specified items that have not yet been identified and quantified, and the impact of future Acquired IPRD charges. To the extent we have quantified the impact of significant R&D charges or other income resulting from upfront or contingent milestone payments in connection with asset acquisitions or licensing of third-party intellectual property rights, we may update this information from time to time on our website www.bms.com, in the "Investors" section. Non-GAAP guidance assumes current exchange rates. The financial guidance is subject to risks and uncertainties applicable to all forward-looking statements as described elsewhere in this press release.

A reconciliation of forward-looking non-GAAP measures, including non-GAAP EPS, to the most directly comparable GAAP measures is not provided because comparable GAAP measures for such measures are not reasonably accessible or reliable due to the inherent difficulty in forecasting and quantifying measures that would be necessary for such reconciliation. Namely, we are not, without unreasonable effort, able to reliably predict the impact of accelerated depreciation and impairment charges, legal and other settlements, gains and losses from equity investments and other adjustments. In addition, the company believes such a reconciliation would imply a degree of precision and certainty that could be confusing to investors. These items are uncertain, depend on various factors and may have a material impact on our future GAAP results. See "Cautionary Statement Regarding Forward-Looking Statements" and "Use of Non-GAAP Financial Information."

Environmental, Social & Governance (ESG)
As a leading biopharmaceutical company, Bristol Myers Squibb’s passion for making an impact extends beyond the discovery, development and delivery of innovative medicines that help patients prevail over serious diseases. To learn more about our priorities and goals, please visit our latest ESG report.

Conference Call Information
Bristol Myers Squibb will host a conference call today, Thursday, October 31, 2024, at 8:00 a.m. ET, during which company executives will review quarterly financial results and address inquiries from investors and analysts. Investors and the general public are invited to listen to a live webcast of the call at View Source." target="_blank" title="View Source." rel="nofollow">View Source

Investors and the public can register for the live conference call here. Those unable to register can access the live conference call by dialing in the U.S. toll-free 1-833-816-1116 or international +1 412-317-0705. Materials related to the call will be available at View Source prior to the start of the conference call.

A replay of the webcast will be available at View Source approximately three hours after the conference call concludes. A replay of the conference call will be available beginning at 11:30 a.m. ET on October 31, 2024, through 11:30 a.m. ET on November 14, 2024, by dialing in the U.S. toll free 1-877-344-7529 or international +1 412-317-0088, confirmation code: 9624003.

On October 31, 2024 Bicycle Therapeutics plc (NASDAQ: BCYC), a pharmaceutical company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported recent business progress and financial results for the third quarter ended September 30, 2024 (Press release, Bicycle Therapeutics, OCT 31, 2024, View Source [SID1234647582]).

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"In the third quarter, we continued to make significant advancements across our business and pipeline. At ESMO (Free ESMO Whitepaper), we reported updated data for our clinical-stage molecules, further supporting their promising monotherapy response rates and differentiated safety profiles. Additionally, last week we shared exciting first human imaging data for our first radiopharmaceuticals molecule, validating the potential of MT1-MMP as a novel cancer target and providing important information on the ability of our Bicycle molecules to deliver radioisotopes to the tumor," said Kevin Lee, Ph.D., CEO of Bicycle Therapeutics. "Altogether, we believe these data demonstrate the power and broad capabilities of our Bicycle technology platform, and we look forward to providing additional updates later this year."

Third Quarter 2024 and Recent Events

· Announced first human imaging data for a Bicycle Radionuclide Conjugate (BRC) targeting MT1-MMP and outlined strategy for leadership in next-generation radiopharmaceuticals.

o Data presented at the European Association of Nuclear Medicine 2024 Congress validate the potential of MT1-MMP as a novel target in the treatment of cancer, demonstrate the translatability of BRC preclinical data and highlight the potential of Bicycle molecules for targeted radionuclide therapy.

§ In an oral presentation, the German Cancer Consortium shared results of fluorine-18-labelled FDG-PET/CT imaging and gallium-68-labelled BRC MT1-MMP PET/CT imaging in a 65-year-old male diagnosed with advanced pulmonary adenocarcinoma, the most common type of non-small cell lung cancer, in the lung and lymph nodes confirmed by endobronchial ultrasound biopsy. Both scans revealed multiple lymph node metastases and bone metastases in the sternum. MT1-MMP imaging demonstrated tracer uptake in the primary tumor in the lung and lymph node and bone metastases, consistent with FDG imaging. Additionally, the MT1-MMP BRC tracer showed renal excretion, with all other organs showing only a negligible tracer uptake. Clear imaging contrast was also observed at early time points.

§ In an e-poster presented by Bicycle Therapeutics, preclinical data demonstrate the suitability of Bicycle molecules to deliver indium to tumors in vivo due to their favorable properties including specific tumor uptake, rapid tumor penetration and rapid renal elimination. Additionally, imaging showed how the biodistribution profile of BRCs can be optimized to maintain high tumor uptake and retention while significantly reducing kidney levels. These data build on the body of preclinical data that the company has published in this area demonstrating the use of Bicycle molecules to effectively deliver various radioisotopes, such as lutetium and lead, to tumors.

o Bicycle Therapeutics’ strategy in radiopharmaceuticals focuses on pursuing novel targets with first-in-class potential and selecting the isotope that best aligns with the target biology and indication. In line with this strategy, the company selected EphA2, a novel tumor antigen that is widely expressed in many cancers, as its second BRC target and signed a letter of intent with leading isotope technology company Eckert & Ziegler to put in place an agreement to supply a range of radioisotopes and develop and manufacture BRC molecules.

· Presented updated clinical results across oncology pipeline at the European Society for Medical Oncology Congress 2024.

o Zelenectide pevedotin (formerly BT8009) is a Bicycle Toxin Conjugate (BTC) molecule targeting Nectin-4, a well-validated tumor antigen. Updated results from the ongoing Phase 1/2 Duravelo-1 trial evaluating 5 mg/m2 weekly of zelenectide pevedotin monotherapy in patients with metastatic urothelial cancer (mUC) who had not previously been treated with enfortumab vedotin showed a 45% overall response rate (ORR) in efficacy-evaluable patients (n=38), with a median duration of response of 11.1 months among patients with confirmed responses (n=14). Zelenectide pevedotin continued to demonstrate an emerging differentiated safety profile, particularly around adverse events of interest such as peripheral neuropathy, skin reactions and eye disorders.

The global Phase 2/3 Duravelo-2 registrational trial of zelenectide pevedotin in patients with mUC is currently enrolling. Additional data updates for zelenectide pevedotin monotherapy in other tumor types and in combination with pembrolizumab in first-line mUC are planned by year end.

o BT5528 is a BTC molecule targeting tumor antigen EphA2, which has historically been difficult to target using other drug conjugate approaches. Updated results from the ongoing Phase 1/2 trial evaluating 6.5 mg/m2 every two weeks and 5 mg/m2 weekly of BT5528 monotherapy in patients with advanced solid tumors showed an emerging differentiated safety profile and antitumor activity, including a 45% ORR in mUC patients enrolled in the dose expansion cohort (n=11) receiving 6.5 mg/m2 every two weeks.

Bicycle Therapeutics is currently assessing BT5528 at 6.5 mg/m2 every two weeks in combination with nivolumab, with results expected in 2025.

o An analysis of BTC clinical data showed that treatment-related peripheral neuropathy (TRPN) in patients receiving either zelenectide pevedotin or BT5528 occurred at low rates and were primarily low grade. In 223 patients from ongoing Phase 1/2 studies, TRPN occurred in 28% of zelenectide pevedotin-treated patients and in 19% of BT5528-treated patients, nearly all of which were low grade (Grade 1-2). One Grade 3 event (neuralgia) was reported in a patient treated with zelenectide pevedotin following prior therapy with enfortumab vedotin, while no Grade 3-4 events were observed for BT5528.

These data showing low rates of TRPN at primarily low severity with BTC molecules support the hypothesis that the antibody-drug construct may be a primary driver of peripheral neuropathy rather than monomethyl auristatin E (MMAE) toxicity as was previously believed.

o BT7480 is a Nectin-4 targeted CD137 agonist designed to overcome immune agonist toxicities and activate the immune system in Nectin-4 expressing tumors. Initial data from the Phase 1/2 dose escalation trial evaluating BT7480 in patients with advanced solid tumors showed an emerging differentiated safety and tolerability profile, with low rates of severe adverse events among 39 patients assigned to receive one of 10 different doses (0.002-3.5 mg/kg weekly). Preliminary biomarker analyses support BT7480 dual targeting of CD137 and Nectin-4 as demonstrated by enhanced immune cell activation, aligned with the proposed mechanism of action of BT7480.

As the maximum tolerated dose for BT7480 has not yet been reached, Bicycle Therapeutics is continuing dose exploration in combination studies, starting with nivolumab.

· Promoted Zafar Qadir to Chief Legal Officer and General Counsel. Since joining Bicycle Therapeutics in April 2020, Mr. Qadir has managed critical responsibilities to support the company’s growth by leading the legal, compliance and intellectual property functions. Over the course of his career, Mr. Qadir has more than a decade of corporate, legal, intellectual property, regulatory and compliance experience and has played a pivotal role in Bicycle Therapeutics’ key partnerships and transactions.

Third Quarter 2024 Financial Results

· Cash and cash equivalents were $890.9 million as of September 30, 2024, compared to $526.4 million as of December 31, 2023. The increase in cash and cash equivalents is primarily due to net proceeds from our PIPE financing in May 2024 and share option exercises, offset by the repayment of our debt facility with Hercules Capital, Inc. in July 2024 and cash used in operating activities.

· Research and Development (R&D) expenses were $48.3 million for the three months ended September 30, 2024, compared to $39.9 million for the three months ended September 30, 2023. The increase in expense of $8.4 million was primarily due to increased clinical program expenses for zelenectide pevedotin development and increased personnel-related expenses, including incremental share-based compensation of $1.1 million, offset by decreased clinical program expenses for Bicycle Tumor-Targeted Immune Cell Agonist molecule development, lower discovery, platform and other expenses, and higher U.K. R&D tax credits period over period.

· General and administrative expenses were $18.3 million for the three months ended September 30, 2024, compared to $16.3 million for the three months ended September 30, 2023. The increase of $2.0 million was primarily due to increased personnel-related expenses, including incremental share-based compensation expense of $0.7 million.

· Net loss was $50.8 million, or $(0.74) basic and diluted net loss per share, for the three months ended September 30, 2024, compared to net loss of $49.9 million, or $(1.26) basic and diluted net loss per share, for three months ended September 30, 2023.