Prothena Corporation plc: Prothena Reports Third Quarter 2024 Financial Results and Business Highlights

• Net cash used in operating and investing activities was $45.2 million and $102.5 million for the third quarter and first nine months of 2024, respectively; quarter-end cash and restricted cash position was $520.1 million
• PRX012, a potential single-injection once-monthly subcutaneous treatment, is designed to address the unmet need of millions of patients with presymptomatic or early symptomatic Alzheimer's disease; Prothena expects to report multiple clinical readouts starting in mid-2025 and continuing throughout the year from the ongoing Phase 1 ASCENT clinical trials
• Results from partner Roche evaluating prasinezumab in patients with early Parkinson's disease from the Phase 2 PASADENA OLE clinical trial published in Nature Medicine
• In collaboration with Bristol Myers Squibb, Prothena has initiated a Phase 1 clinical trial for PRX019, a potential treatment for neurodegenerative diseases
• With partner Novo Nordisk, Phase 1 clinical trial results for coramitug (formerly PRX004) in patients with ATTR amyloidosis published in Amyloid, the official journal of the ISA
• Prothena appointed Chad J. Swanson, Ph.D., as Chief Development Officer

Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical biotechnology company with a robust pipeline of investigational therapeutics built on protein dysregulation expertise, today reported financial results for the third quarter and first nine months of 2024 and provided business highlights.

"Within the next several quarters we expect meaningful data readouts on four clinical programs in our robust R&D pipeline that have the potential to significantly improve the lives of millions of individuals with neurodegenerative or rare peripheral amyloid diseases and their families," said Gene Kinney, Ph.D., President and Chief Executive Officer, Prothena. "From our wholly-owned programs we expect to complete our confirmatory Phase 3 AFFIRM-AL clinical trial evaluating birtamimab, which is being conducted under a SPA agreement with the FDA at a significance level of 0.10, in 1H 2025. We also expect to announce multiple clinical readouts from our ongoing Phase 1 ASCENT clinical trials evaluating PRX012 for Alzheimer's disease starting in mid-2025 and continuing throughout the year. In collaboration with Roche, we expect results from the Phase 2b PADOVA clinical trial evaluating prasinezumab for Parkinson's disease in 4Q 2024 and with Novo Nordisk, we expect results from the Phase 2 signal-detection clinical trial evaluating coramitug for ATTR amyloidosis with cardiomyopathy in 1H 2025."

Third Quarter, Recent Business Highlights and Upcoming Milestones

Neurodegenerative Diseases Portfolio

Alzheimer's Disease

PRX012, a wholly-owned potential best-in-class, single-injection once-monthly antibody delivered subcutaneously for the treatment of Alzheimer's disease that targets a key epitope at the N-terminus of amyloid beta (Aß) with high binding potency. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for PRX012 for the treatment of Alzheimer's disease.

• Designed as a potential single-injection once-monthly subcutaneous treatment to address the unmet need of millions of patients with presymptomatic or early symptomatic Alzheimer's disease, Prothena expects to report multiple clinical readouts starting in mid-2025 and continuing throughout the year from the ongoing Phase 1 ASCENT clinical trials
• Prothena has currently enrolled approximately 260 patients in the ASCENT clinical trials
• Poster presentation at CTAD 2024 highlighted the clinical trial design and patient demographic diversity of the ongoing ASCENT clinical trials

BMS-986446 (formerly PRX005), a potential best-in-class antibody for the treatment of Alzheimer's disease that specifically targets a key epitope within the microtubule binding region (MTBR) of tau, a protein implicated in the causal pathophysiology of Alzheimer's disease.

• Bristol Myers Squibb continues to enroll the ongoing Phase 2 clinical trial in approximately 475 patients with early Alzheimer's disease; primary completion expected in 2027 (NCT06268886)
• Bristol Myers Squibb is responsible for all development, manufacturing, and commercialization
• Oral encore presentation by partner Bristol Myers Squibb at CTAD 2024 highlighted the design of the ongoing Phase 2 TargetTau-1 clinical trial

PRX123, a wholly-owned potential first-in-class dual Aß/tau vaccine designed for the treatment and prevention of Alzheimer's disease, is a dual-target vaccine targeting key epitopes within the N-terminus of Aß and MTBR-tau designed to promote amyloid clearance and block the transmission of pathogenic tau. The FDA cleared the investigational new drug (IND) application and granted Fast Track designation for PRX123 for the treatment of Alzheimer's disease.

• Continuing to optimize capital allocation across our robust R&D pipeline, Prothena expects to update plans for Phase 1 clinical trial in 2025

Parkinson's Disease

Prasinezumab, a potential first-in-class antibody for the treatment of Parkinson's disease that is designed to target key epitopes within the C-terminus of alpha-synuclein and is the focus of a worldwide collaboration with Roche.

• PASADENA Open Label Extension Phase 2 clinical trial results published in Nature Medicineshowed a continued reduction in motor and functional progression compared to real-world data after 4 years
• Topline results from Phase 2b PADOVA clinical trial in patients with early Parkinson's disease, which has completed enrollment of 586 patients, expected in 4Q 2024 (NCT04777331)

Neurodegenerative Diseases

PRX019, a potential treatment of neurodegenerative diseases in development in collaboration with Bristol Myers Squibb.

• Prothena has initiated a Phase 1 first-in-human clinical trial to evaluate the safety, tolerability, immunogenicity, and pharmacokinetics of single ascending and multiple doses in healthy adults

Rare Peripheral Amyloid Diseases Portfolio

AL Amyloidosis

Birtamimab, a wholly-owned potential best-in-class anti-amyloid antibody for the treatment of AL amyloidosis designed to directly neutralize soluble toxic light chain aggregates and promote clearance of amyloid that causes organ dysfunction and failure. Among patients with AL amyloidosis, a rare, progressive, and fatal disease, newly diagnosed individuals with cardiac involvement are at the highest risk for early death. Birtamimab has been granted Fast Track designation by the FDA and has been granted Orphan Drug Designation by both the FDA and European Medicines Agency. A significant survival benefit was observed in the post hoc analysis of birtamimab-treated patients categorized as Mayo Stage IV at baseline in the previous Phase 3 VITAL clinical trial (Blood 2023

• The ongoing confirmatory Phase 3 AFFIRM-AL clinical trial is being conducted under a Special Protocol Assessment (SPA) agreement with the FDA with a primary endpoint of all-cause mortality (time-to-event) at a significance level of 0.10
• Topline results from confirmatory AFFIRM-AL Phase 3 clinical trial expected in 1H 2025 (NCT04973137)

ATTR Amyloidosis

Coramitug (formerly PRX004), a potential first-in-class amyloid depleter antibody for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM) designed to deplete the pathogenic, non-native forms of the transthyretin (TTR) protein, is being developed by Novo Nordisk as part of its up to $1.2 billion acquisition of Prothena's ATTR amyloidosis business and pipeline.

• Phase 1 clinical trial results for coramitug in patients with ATTR amyloidosis published in Amyloid,the official journal of the International Society of Amyloidosis
• Ongoing Phase 2 signal-detection clinical trial in patients with ATTR-CM is being conducted by Novo Nordisk
• Phase 2 clinical trial has completed enrollment of approximately 99 patients with topline data expected in 1H 2025 (NCT05442047)

Corporate Highlight

• Prothena announced the appointment of Chad J. Swanson, Ph.D., as Chief Development Officer in September 2024, leading all clinical development and medical functions. Dr. Swanson is a neuropharmacologist with over 20 years industry experience and joined Prothena as Senior Vice President and Head of Clinical Development in January 2023 from Eisai, Inc. where he was the Executive Director of Clinical Research in the Alzheimer's Disease Brain Health group.

Third Quarter and First Nine Months of 2024 Financial Results

For the third quarter and first nine months of 2024, Prothena reported net loss of $59.0 million and $64.4 million, respectively, as compared to a net income of $21.9 million and net loss of $79.6 million for the third quarter and first nine months of 2023, respectively. Net loss per share was $1.10 and $1.20 for the third quarter and first nine months of 2024, as compared to a net income per share on a diluted basis of $0.38 and a net loss per share of $1.50 for the third quarter and first nine months of 2023, respectively.

Prothena reported total revenue of $1.0 million and $133.0 million for the third quarter and first nine months of 2024, respectively, as compared to total revenue of $84.9 million and $91.1 million for the third quarter and first nine months of 2023, respectively. Total revenue for the third quarter and first nine months of 2024 was primarily from collaboration revenue from Bristol Myers Squibb as compared to total revenue for the third quarter and first nine months of 2023 that was also primarily from collaboration revenue from Bristol Myers Squibb.

Research and development (R&D) expenses totaled $50.7 million and $172.3 million for the third quarter and first nine months of 2024, respectively, as compared to $57.9 million and $158.7 million for the third quarter and first nine months of 2023, respectively. The decrease in R&D expenses for the third quarter compared to the same period in the prior year was primarily due to lower manufacturing expenses. The increase in R&D expenses for the first nine months of 2023, compared to the same period in the prior year was primarily due to higher clinical trial expenses and higher personnel related expenses; offset in part by lower manufacturing and other R&D expenses. R&D expenses included non-cash share-based compensation expense of $5.1 million and $16.2 million for the third quarter and first nine months of 2024, respectively, as compared to $4.9 million and $14.2 million for the third quarter and first nine months of 2023, respectively.

General and administrative (G&A) expenses totaled $16.8 million and $50.4 million for the third quarter and first nine months of 2024, respectively, as compared to $16.6 million and $44.9 million for the third quarter and first nine months of 2023, respectively. The increase in G&A expenses for the first nine months of 2024 compared to the same period in the prior year was primarily related to higher personnel related expenses. G&A expenses included non-cash share-based compensation expense of $5.9 million and $19.2 million for the third quarter and first nine months of 2024, respectively, as compared to $6.0 million and $15.7 million for the third quarter and first nine months of 2023, respectively.

Total non-cash share-based compensation expense was $11.0 million and $35.4 million for the third quarter and first nine months of 2024, respectively, as compared to $10.9 million and $29.8 million for the third quarter and first nine months of 2023, respectively.

As of September 30, 2024, Prothena had $520.1 million in cash, cash equivalents and restricted cash, and no debt.

As of November 6, 2024, Prothena had approximately 53.8 million ordinary shares outstanding.

2024 Financial Guidance

The Company continues to expect full year 2024 net cash used in operating and investing actives to be $148 to $160 million and expects to end the year with approximately $468 million (midpoint) in cash, cash equivalents and restricted cash. The estimated full year 2024 net cash used from operating and investing activities is primarily driven by an estimated net loss of $120 to $135 million, which includes an estimated $48 million of non-cash share-based compensation expense.

About Prothena

Prothena Corporation plc is a late-stage clinical biotechnology company with expertise in protein dysregulation and a pipeline of investigational therapeutics with the potential to change the course of devastating neurodegenerative and rare peripheral amyloid diseases. Fueled by its deep scientific expertise built over decades of research, Prothena is advancing a pipeline of therapeutic candidates for a number of indications and novel targets for which its ability to integrate scientific insights around neurological dysfunction and the biology of misfolded proteins can be leveraged. Prothena's pipeline includes both wholly-owned and partnered programs being developed for the potential treatment of diseases including AL amyloidosis, ATTR amyloidosis with cardiomyopathy, Alzheimer's disease, Parkinson's disease and a number of other neurodegenerative diseases. For more information, please visit the Company's website at www.prothena.com and follow the Company on Twitter @ProthenaCorp.

Forward-Looking Statements

This press release contains forward-looking statements. These statements relate to, among other things, the sufficiency of our cash position to fund advancement of a broad pipeline and completion of our ongoing clinical trials; the continued advancement of our discovery, preclinical, and clinical pipeline, and expected milestones in 2024, 2025, and beyond; the treatment potential, designs, proposed mechanisms of action, and potential administration of PRX012, BMS-986446/PRX005, PRX123, prasinezumab, PRX019, birtamimab, and coramitug/PRX004; plans for ongoing and future clinical trials of PRX012, BMS-986446/PRX005, PRX123, prasinezumab, PRX019, birtamimab, and coramitug/PRX004; the expected timing of reporting data from clinical trials, including multiple clinical readouts starting in mid- 2025 and continuing throughout the year from our ongoing Phase 1 clinical trials evaluating PRX012 and topline study results for our Phase 3 AFFIRM-AL clinical trial between in 1H 2025; our anticipated net cash burn from operating and investing activities for 2024 and expected cash balance at the end of 2024; and our estimated net loss and non-cash share-based compensation expense for 2024. These statements are based on estimates, projections and assumptions that may prove not to be accurate, and actual results could differ materially from those anticipated due to known and unknown risks, uncertainties and other factors, including but not limited to those described in the "Risk Factors" sections of our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 12, 2024, and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the SEC. We undertake no obligation to update publicly any forward-looking statements contained in this press release as a result of new information, future events, or changes in our expectations.

PROTHENA CORPORATION PLC CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (unaudited amounts in thousands except per share data)
		Three Months Ended September 30,								Nine Months Ended September 30,
			2024				2023				2024				2023
Collaboration revenue			970				84,866				132,984				91,004
Revenue from license and intellectual property											50				50
Total revenue			970				84,866				133,034				91,054
Operating expenses:
Research and development			50,723				57,913				172,347				158,680
General and administrative			16,760				16,645				50,351				44,895
Total operating expenses			67,483				74,558				222,698				203,575
Income (loss) from operations			(66,513				10,308				(89,664				(112,521
Total other income, net			6,677				8,507				20,235				22,659
Income (loss) before income taxes			(59,836				18,815				(69,429				(89,862
Benefit from income taxes			(835				(3,092				(5,075				(10,310
Net income (loss)			(59,001				21,907				(64,354				(79,552
Basic net income (loss) per ordinary share			(1.10				0.41				(1.20				(1.50
Diluted net income (loss) per ordinary share			(1.10				0.38				(1.20				(1.50
Shares used to compute basic net income (loss) per share			53,790				53,559				53,757				53,064
Shares used to compute diluted net income (loss) per share			53,790				58,004				53,757				53,064

PROTHENA CORPORATION PLC CONDENSED CONSOLIDATED BALANCE SHEETS (unaudited amounts in thousands)
	September 30,			December 31,
		2024			2023
Assets
Cash and cash equivalents		519,262			618,830
Restricted cash, current					1,352
Prepaid expenses and other current assets		15,722			19,100
Total current assets		534,984			639,282
Property and equipment, net		3,254			3,836
Operating lease right-of-use assets		11,400			12,162
Restricted cash, non-current		860			860
Other non-current assets		44,756			40,242
Total non-current assets		60,270			57,100
Total assets		595,254			696,382
Liabilities and Shareholders' Equity
Accrued research and development		10,340			14,724
Deferred revenue, current		8,832
Lease liability, current		2,613			1,114
Other current liabilities		24,637			41,053
Total current liabilities		46,422			56,891
Deferred revenue, non-current		5,589			67,405
Lease liability, non-current		8,881			10,721
Total non-current liabilities		14,470			78,126
Total liabilities		60,892			135,017
Total shareholders' equity		534,362			561,365
Total liabilities and shareholders' equity		595,254			696,382

View source version on businesswire.com: https://www.businesswire.com/news/home/20241112238826/en/

Contacts:

Investors
Mark Johnson, CFA, Vice President, Investor Relations
650-417-1974, [e-mail]

Media
Michael Bachner, Senior Director, Corporate Communications
609-664-7308, [e-mail]