On May 11, 2021 Dynavax Technologies Corporation ("Dynavax") (Nasdaq: DVAX) reported the pricing of $200.0 million aggregate principal amount of 2.50% convertible senior notes due 2026 (the "notes") in a private placement to persons reasonably believed to be qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Press release, Dynavax Technologies, MAY 11, 2021, View Source [SID1234579684]). Dynavax also granted the initial purchasers of the notes an option to purchase up to an additional $30.0 million aggregate principal amount of notes. The sale of the notes is expected to close on May 13, 2021, subject to customary closing conditions.

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The notes will be general unsecured obligations of Dynavax and will accrue interest payable semiannually in arrears on May 15 and November 15 of each year, beginning on November 15, 2021, at a rate of 2.50% per year. The notes will mature on May 15, 2026, unless earlier converted, redeemed or repurchased. The initial conversion rate of the notes will be 95.5338 shares of Dynavax’s common stock per $1,000 principal amount of notes (equivalent to an initial conversion price of approximately $10.47 per share of Dynavax’s common stock). The initial conversion price of the notes represents a premium of approximately 32.5% over the last reported sale price of Dynavax’s common stock on May 10, 2021. The notes will be convertible by the holders thereof into cash, shares of Dynavax’s common stock or a combination of cash and shares of Dynavax’s common stock, at Dynavax’s election.

Dynavax may redeem for cash all or any portion of the notes, at its option on or after May 20, 2024 and prior to the 31st scheduled trading day immediately preceding the maturity date, if the last reported sale price of Dynavax’s common stock has been at least 130% of the conversion price then in effect for at least 20 trading days (whether or not consecutive) during any 30 consecutive trading day period (including the last trading day of such period) ending on, and including, the trading day immediately preceding the date on which Dynavax provides notice of redemption, at a redemption price equal to 100% of the principal amount of the notes to be redeemed, plus accrued and unpaid interest to, but excluding, the redemption date.

If Dynavax undergoes a "fundamental change" (as defined in the indenture governing the notes), subject to certain conditions and exceptions, noteholders may require Dynavax to repurchase for cash all or any portion of their notes at a fundamental change repurchase price equal to 100% of the principal amount of the notes to be repurchased, plus accrued and unpaid interest to, but excluding, the fundamental change repurchase date. In addition, following certain corporate events that occur prior to the maturity date or if Dynavax delivers a notice of redemption, Dynavax will, in certain circumstances, increase the conversion rate for a noteholder who elects to convert its notes in connection with such a corporate event or convert its notes called (or deemed called) for redemption in connection with such notice of redemption, as the case may be.

Dynavax estimates that the net proceeds from the offering of the notes will be approximately $195.1 million (or approximately $224.4 million if the initial purchasers exercise their option to purchase additional notes in full), after deducting the initial purchasers’ discounts and commissions and estimated offering expenses payable by Dynavax. Dynavax expects to use the net proceeds from the offering of the notes, together with cash on hand, to repay in full the outstanding debt and other obligations under Dynavax’s term loan agreement and to pay the costs of the capped call transactions described below. Dynavax expects that approximately $190.2 million will be needed to repay the outstanding debt and other obligations under the term loan agreement and approximately $24.2 million will be needed to pay the cost of the capped call transactions.

If the initial purchasers exercise their option to purchase additional notes in full, Dynavax expects to use approximately $3.6 million of the net proceeds from the sale of such additional notes to enter into additional capped call transactions. Dynavax expects to use any remaining net proceeds from the sale of such additional notes for general corporate purposes.

In connection with the pricing of the notes, Dynavax entered into capped call transactions with one of the initial purchasers and other financial institutions (the "option counterparties"). The capped call transactions will cover, subject to customary adjustments, the number of shares of Dynavax’s common stock that initially underlie the notes. The capped call transactions are expected to offset the potential dilution to Dynavax’s common stock as a result of any conversion of notes, with such offset subject to a cap initially equal to $15.80 (which represents a premium of 100% over the last reported sale price of Dynavax’s common stock on May 10, 2021).

In connection with establishing their initial hedges of the capped call transactions, Dynavax has been advised that the option counterparties and/or their respective affiliates expect to enter into various derivative transactions with respect to Dynavax’s common stock concurrently with or shortly after the pricing of the notes and/or purchase shares of Dynavax’s common stock concurrently with or shortly after the pricing of the notes. This activity could increase (or reduce the size of any decrease in) the market price of Dynavax’s common stock or the trading price of the notes at that time.

In addition, the option counterparties and/or their respective affiliates may modify their hedge positions by entering into or unwinding various derivatives with respect to Dynavax’s common stock and/or purchasing or selling Dynavax’s common stock or other securities of Dynavax in secondary market transactions following the pricing of the notes and prior to the maturity of the notes (and are likely to do so on each exercise date of the capped call transactions, which are expected to occur during the 30 trading day period beginning on the 31st scheduled trading day prior to the maturity date of the notes, or following any termination of any portion of the capped call transactions in connection with any repurchase, redemption or early conversion of the notes). This activity could also cause or avoid an increase or a decrease in the market price of Dynavax’s common stock or the notes, which could affect a noteholder’s ability to convert its notes and, to the extent the activity occurs during any observation period related to a conversion of notes, it could affect the amount and value of the consideration that a noteholder will receive upon conversion of such notes.

Neither the notes, nor any shares of Dynavax’s common stock issuable upon conversion of the notes, have been registered under the Securities Act or any state securities laws, and unless so registered, may not be offered or sold in the United States absent registration or an applicable exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and other applicable securities laws.

This press release is neither an offer to sell nor a solicitation of an offer to buy any securities, nor shall it constitute an offer, solicitation or sale of the securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction.

On May 11, 2021 Aptevo Therapeutics Inc. ("Aptevo" or "the Company") (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported its financial results for the quarter ended March 31, 2021 (Press release, Aptevo Therapeutics, MAY 11, 2021, View Source [SID1234579700]).

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"We are pleased to report progress in the clinical trial of our ADAPTIR platform candidate APVO436, with the dose limiting toxicity (DLT) evaluation in cohorts 1 through 9 now completed and 44 patients enrolled to date in cohorts 1-10. We remain confident in the clinical impact potential of APVO436 and our platform technologies, and look forward to sharing interim data readouts from our ongoing APVO436 study later this year," said Mr. Marvin White, President and CEO of Aptevo. "The transaction with HCR, which we completed in March 2021, provided significant non-dilutive funding, which adds to our cash runway and helps fund the company through the next twelve months."

First Quarter 2021 Financial Results Summary

As announced in March, Aptevo received $35 million ("the Investment Amount") from its sale of the right to royalty payments made by Pfizer Inc. ("Pfizer") with respect to net sales of RUXIENCE to an entity managed by HealthCare Royalty Management, LLC ("HCR"). Aptevo is eligible to receive additional payments in aggregate of up to an additional $32.5 million based on the achievement of sales milestones in 2021, 2022, and 2023 (collectively, the "Milestone Amounts"). The Royalty Purchase Agreement further provides that, once HCR reaches aggregate royalty payments totaling 190% of the Investment Amount plus the Milestone Amounts to the extent paid by HCR to the Company, Aptevo will be entitled to receive 50% of any additional royalty payments by Pfizer thereafter. In connection with this royalty purchase agreement, Aptevo amended its term loan agreement with MidCap Financial and used $10 million of the proceeds received to pay down outstanding principal.

Cash Position: Aptevo had cash and cash equivalents as of March 31, 2021 totaling $58.8 million, including restricted cash of $1.3 million. The restricted cash is expected to be released over the next twelve months.

Royalty Revenue: Royalty revenue was $2.4 million for the three months ended March 31, 2021, related to the royalty from Pfizer on global net sales of RUXIENCE, a biosimilar to the drug RITUXAN, launched by Pfizer in early 2020. RUXIENCE is a trademark of Pfizer; RITUXAN is a trademark of Biogen. Due to our continuing involvement under the Definitive Agreement originally between Trubion and Wyeth, we continue to recognize royalty revenue on net sales of RUXIENCE and record the royalty payments to HCR as a reduction of the liability when paid. As such payments are made to HCR, the balance of the liability will be effectively repaid over the life of the Royalty Purchase Agreement.

Research and Development Expenses: Research and development expenses increased to $5.4 million for the three months ended March 31, 2021 from $4.0 million for the three months ended March 31, 2020 as we continue to invest in the APVO436 clinical trial and our preclinical candidates, including ALG.APV-527, APVO603 and APVO442.

General and Administrative Expenses: For the three months ended March 31, 2021, general and administrative expenses increased to $3.9 million from $3.6 million for March 31, 2020, with higher costs for professional services.

Other Expense, Net: Other expense, net consists primarily of interest on debt and costs related to debt extinguishment. Other expense, net was $0.8 million for the three months ended March 31, 2021 and $2.4 million for the three months ended March 31, 2020. A slight increase in interest expense this quarter was offset by a significant decrease due to a loss on extinguishment of debt of $2.1 million recognized in the first quarter of 2020 when we repaid our previous loan to MidCap Financial using the proceeds from the sale of Aptevo BioTherapeutics LLC.

Discontinued Operations: Income from discontinued operations was $0.4 million for the three months ended March 31, 2021 and $12.9 million for the three months ended March 31, 2020. For the three months ended March 31, 2021, we collected a deferred payment of $0.2 million from Medexus related to fourth quarter 2020 IXINITY sales and $0.2 million from the Saol Therapeutics, related to the 2017 sale of the Hyperimmune Business to them. For the three months ended March 31, 2020, we recognized net income from discontinued operations totaling $12.9 million. This included the gain on the sale of Aptevo BioTherapeutics LLC of $14.3 million and net operating losses from Aptevo BioTherapeutics LLC of $1.6 million related to the period prior to the sale on February 28, 2020.

Net Income (Loss): Aptevo’s net loss for the three-month period ended March 31, 2021 was $(7.3) million or $(1.64) per share, as compared to a net income of $2.9 million or $0.89 per share for the corresponding period in 2019. Our net loss from continuing operations for the first quarter of 2021 was $(7.6) million compared to $(10.0) million in the first quarter of 2020.

Liability Related to Sale of Future Royalties: We treat the Royalty Purchase Agreement with HCR as a debt financing, amortized under the effective interest rate method over the estimated life of the related expected royalty stream. The liabilities related to sale of future royalties and the debt amortization are based on our current estimates of future royalties expected to be paid over the life of the arrangement. We will periodically assess the expected royalty payments using projections from external sources. To the extent our estimates of future royalty payments are greater or less than previous estimates or the estimated timing of such payments is materially different than previous estimates, we will adjust the effective interest rate and recognize related non-cash interest expense on a prospective basis. We are not obligated to repay the proceeds received under the Royalty Purchase Agreement with HCR.

On May 11, 2021 Ultimovacs ASA ("Ultimovacs") (OSE ULTI), a clinical stage leader in immune stimulatory vaccines for cancer, reported the publication in Frontiers in Immunology of its positive long-term Overall Survival (OS) data from the Phase I trial evaluating the Company’s universal cancer vaccine, UV1, in combination with checkpoint inhibitor ipilimumab in patients with metastatic malignant melanoma (Press release, Ultimovacs, MAY 11, 2021, View Source [SID1234579716]). As published in the journal, in addition to the achievement of the primary endpoints of safety and tolerability, 50% of the patients were still alive at the data cut-off, supporting the combination of the Company’s proprietary UV1 vaccine with ipilimumab, a CTLA-4 checkpoint inhibitor and standard-of-care treatment, in this late-stage patient population.

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"Publishing our clinical trial data in such a prestigious peer-reviewed publication adds validation for UV1 as a promising therapeutic option for cancer patients. As we continue to evaluate UV1 in various combinations and indications, it is valuable to gain increased international recognition from the clinical community for this study," stated Jens Bjørheim, Chief Medical Officer at Ultimovacs. "Historical data on the use of ipilimumab as monotherapy in malignant melanoma have shown a 5-year survival rate below 20%, therefore the results published today reinforce UV1’s potential in this indication."

The data published in Frontiers in Immunology covers 4.8 years of follow-up on the total of 12 metastatic malignant melanoma patients that were enrolled in the Phase I trial. As reported in the journal, the OS was 50% at 4.8 years, which was confirmed by the results of 5 years of follow-up announced by the Company in December 2020.

Building on these promising Phase I results, Ultimovacs is currently enrolling INITIUM, its Phase II clinical trial evaluating UV1 in combination with ipilimumab and nivolumab in patients with metastatic malignant melanoma. The company expects to announce data on the trial’s primary endpoint in 2H2022. In addition, Ultimovacs has an ongoing and fully-enrolled Phase I trial evaluating UV1 in combination with pembrolizumab, a PD-1 checkpoint inhibitor, as a first line treatment in metastatic malignant melanoma patients.

The publication in Frontiers in Immunology can be found under doi: 10.3389/fimmu.2021.663865.

About UV1

UV1 is a peptide-based vaccine inducing a specific T cell response against the universal cancer antigen telomerase. UV1 is being developed as an "off-the-shelf" therapeutic cancer vaccine which may serve as a platform for use in combination with other immunotherapy which requires an ongoing T cell response for their mode of action. To date, UV1 has been tested in four phase I clinical trials in a total of 82 patients and maintained a positive safety and tolerability profile as well as encouraging signals of efficacy.

About UV1 Clinical Programs

As a universal cancer vaccine, UV1’s unique mechanism of action has the potential to be applicable across most cancer types. The clinical development of the UV1 vaccine includes four randomized, multinational, Phase II combination trials: INITIUM, NIPU, DOVACC and FOCUS, recruiting over 500 patients in total. The INITIUM trial is an Ultimovacs-sponsored clinical trial recruiting 154 patients with metastatic malignant melanoma to evaluate UV1 in combination with ipilimumab and nivolumab as first-line treatment. The NIPU study is testing UV1 in combination with checkpoint inhibitors ipilimumab and nivolumab as second-line treatment in 118 patients with advanced malignant pleural mesothelioma, a rare lung cancer. The study is sponsored by Oslo University Hospital and Bristol-Myers Squibb is providing the checkpoint inhibitors for this study. The DOVACC study is sponsored by the Nordic Society of Gynaecological Oncology. In total, 184 patients with high-grade ovarian cancer will be enrolled to evaluate UV1 in combination with durvalumab and olaparib, both provided by AstraZeneca. FOCUS is an investigator-sponsored, randomized clinical trial enrolling 75 patients with metastatic head and neck cancer receiving pembrolizumab as standard of care, and will evaluate the impact of adding UV1 to this regimen. Ultimovacs anticipates announcing data on the primary endpoints for the NIPU and INITIUM studies in 2H2022 and for the DOVACC and FOCUS studies in 2023.

On May 11, 2021 Verastem, Inc. (Nasdaq: VSTM) (also known as Verastem Oncology), a biopharmaceutical company committed to advancing new medicines for patients battling cancer, reported financial results for the three months ended March 31, 2021, highlighted recent progress and outlined key corporate objectives (Press release, Verastem, MAY 11, 2021, View Source [SID1234579808]).

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"During the first quarter of 2021, we expanded the selection portion of the Phase 2 RAMP 201 study to include all recurrent low-grade serous ovarian cancer types. This decision was based on the positive updated data from the LGSOC cohort of the Phase 1/2 FRAME which continues to show strong response rates across both KRAS mutant and wild-type recurrent LGSOC, along with robust durability and a favorable tolerability profile," said Brian Stuglik, Chief Executive Officer of Verastem Oncology. "We closed the first quarter with just over $127 million in cash, cash equivalent and investments, leaving us well positioned to execute on our two ongoing Phase 2 studies evaluating VS-6766 and defactinib in LGSOC and KRAS G12V non-small cell lung cancer (NSCLC), as well as our other key corporate objectives."

Recent Corporate Highlights

LGSOC

Reported updated data from the LGSOC cohort of the ongoing, investigator-sponsored Phase 1/2 FRAME study evaluating VS-6766 in combination with defactinib in patients with recurrent LGSOC. Combination continues to demonstrate activity, durability and a favorable tolerability profile, including in patients who have progressed following treatment with a MEK inhibitor.

Overall response rate (ORR) across all patients was 52% (11 of 21 patients).

ORR for patients with KRAS mutant LGSOC was 70% (7 of 10 patients).

ORR for patients with wild type LGSOC was 44% (4 of 9 patients).

The most common side effects were Grade 1/2 rash, creatine kinase elevation, nausea, hyperbilirubinemia and diarrhea, which were reversible.
Company-sponsored, registration-directed Phase 2 study (RAMP 201) underway investigating VS-6766 alone and in combination with defactinib for the treatment of recurrent LGSOC. Study recently expanded to include both KRAS mutant and KRAS wild-type patients in the selection phase to determine the optimal go-forward regimen for both types of LGSOC.
KRAS G12V Mutant NSCLC

Company-sponsored, registration-directed Phase 2 study (RAMP 202) underway investigating VS-6766 alone and in combination with defactinib for the treatment of patients with KRAS G12V mutant NSCLC.
Upcoming Milestones and Key Priorities for 2021-2022

LGSOC

Updated data from Phase 1/2 FRAME study to be submitted for presentation at a major medical meeting during the second half of 2021.
Complete selection portion of RAMP 201 during first half of 2022; commence expansion portion.
G12V NSCLC

Complete selection portion of RAMP 202 during first half of 2022; commence expansion portion.
First Quarter 2021 Financial Results

Verastem Oncology ended the first quarter 2021 with cash, cash equivalents and investments of $127.1 million.

Total revenue for the three months ended March 31, 2021 (2021 Quarter) was $1.0 million, compared to $5.1 million for the three months ended March 31, 2020 (2020 Quarter).

Total operating expenses for the 2021 Quarter were $15.1 million, compared to $31.4 million for the 2020 Quarter.

Selling, general and administrative expenses for the 2021 Quarter were $6.2 million, compared to $19.6 million for the 2020 Quarter. The decrease of $13.4 million, or 68.4%, primarily resulted from the Company’s shift in strategic direction and COPIKTRA sale to Secura Bio, Inc., which led to lower employee related expenses and consulting and professional fees.

Research and development expense for the 2021 Quarter was $8.9 million, compared to $10.9 million for the 2020 Quarter. The decrease of $2.0 million, or 18.3%, was primarily related to the upfront non-refundable payment of $3.0 million to Chugai Pharmaceutical Co., Ltd for the VS-6766 license in the 2020 Quarter and decreased contract research organization costs, partially offset by increased drug substance and drug product costs and increased investigator sponsored trial expenses.

Net loss for the 2021 Quarter was $15.0 million, or $0.09 per share (basic and diluted), compared to $38.0 million, or $0.35 per share (basic and diluted), for the 2020 Quarter.

For the 2021 Quarter, non-GAAP adjusted net loss was $12.4 million, or $0.07 per share (diluted), compared to non-GAAP adjusted net loss of $21.3 million, or $0.20 per share (diluted), for the 2020 Quarter. Please refer to the GAAP to Non-GAAP Reconciliation attached to this press release.

Financial Guidance and Outlook

With the proceeds from the sale of COPIKTRA, Verastem Oncology expects that it will have a cash runway until at least 2024 to deliver on the current programs for VS-6766 and defactinib, including clinical and regulatory milestones and development in LGSOC and KRAS mutant NSCLC. Verastem Oncology expects its 2021 annual operating expenses to be approximately $50 million.

Use of Non-GAAP Financial Measures

To supplement Verastem Oncology’s condensed consolidated financial statements, which are prepared and presented in accordance with generally accepted accounting principles in the United States (GAAP), the Company uses the following non-GAAP financial measures in this press release: non-GAAP adjusted net loss and non-GAAP net loss per share. These non-GAAP financial measures exclude certain amounts or expenses from the corresponding financial measures determined in accordance with GAAP. Management believes this non-GAAP information is useful for investors, taken in conjunction with the Company’s GAAP financial statements, because it provides greater transparency and period-over-period comparability with respect to the Company’s operating performance and can enhance investors’ ability to identify operating trends in the Company’s business. Management uses these measures, among other factors, to assess and analyze operational results and trends and to make financial and operational decisions. Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used to supplement an understanding of the Company’s operating results as reported under GAAP, not in isolation or as a substitute for, or superior to, financial information prepared and presented in accordance with GAAP. In addition, these non-GAAP financial measures are unlikely to be comparable with non-GAAP information provided by other companies. The determination of the amounts that are excluded from non-GAAP financial measures is a matter of management judgment and depends upon, among other factors, the nature of the underlying expense or income amounts. Reconciliations between these non-GAAP financial measures and the most comparable GAAP financial measures for the three months ended March 31, 2021 and 2020 are included in the tables accompanying this press release after the unaudited condensed consolidated financial statements.

About VS-6766

VS-6766 (formerly known as CH5126766 and RO5126766) is a unique inhibitor of the RAF/MEK signaling pathway. In contrast to other MEK inhibitors in development, VS-6766 blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows VS-6766 to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors.

About Defactinib

Defactinib (VS-6063) is an oral small molecule inhibitor of FAK and PYK2 that is currently being evaluated as a potential combination therapy for various solid tumors. The Company has received Orphan Drug designation for defactinib in ovarian cancer and mesothelioma in the US, EU and Australia. Preclinical research by Verastem Oncology scientists and collaborators at world-renowned research institutions has described the effect of FAK inhibition to enhance immune response by decreasing immuno-suppressive cells, increasing cytotoxic T cells, and reducing stromal density, which allows tumor-killing immune cells to enter the tumor.1,2

About the VS-6766/Defactinib Combination

RAS mutant tumors are present in ~30% of all human cancers, have historically presented a difficult treatment challenge and are often associated with significantly worse prognosis. Challenges associated with identifying new treatment options for these types of cancers include resistance to single agents, identifying tolerable combination regimens with MEK inhibitors and new RAS inhibitors in development addressing only a minority of all RAS mutated cancers.

The combination of VS-6766 and defactinib has been found to be clinically active in patients with KRAS mt tumors. In an ongoing investigator-initiated Phase 1/2 FRAME study, the combination of VS-6766 and defactinib is being evaluated in patients with LGSOC, KRAS mt NSCLC and colorectal cancer (CRC). The FRAME study was expanded to include new cohorts in pancreatic cancer, KRASmt endometrioid cancer and KRAS-G12V NSCLC. Verastem Oncology is also supporting an investigator-initiated Phase 2 trial evaluating VS-6766 with defactinib in patients with metastatic uveal melanoma.

Verastem Oncology has initiated Phase 2 registration-directed trials of VS-6766 with defactinib in patients with recurrent LGSOC and in patients with recurrent KRAS-G12V NSCLC as part of its RAMP (Raf And Mek Program).

On May 11, 2021 Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical company with a robust pipeline of novel investigational therapeutics built on protein dysregulation expertise, reported financial results for the first quarter of 2021. In addition, the Company provided an update on its R&D programs and 2021 financial guidance (Press release, Prothena, MAY 11, 2021, View Source [SID1234579669]).

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"We recently welcomed Hideki Garren to Prothena as Chief Medical Officer and look forward to his expertise contributing to our transition to a fully integrated research, development and commercial biotechnology company," said Gene Kinney, Ph.D., President and Chief Executive Officer of Prothena. "The oral presentations at AD/PD and AAN highlight the continued translation of our differentiated protein dysregulation scientific platform from preclinical findings to clinical benefit for patients across multiple programs in our portfolio. We remain on track for significant news flow this year with the planned initiation of three late-stage clinical studies for birtamimab, prasinezumab and PRX004. We will advance two programs in our Alzheimer’s portfolio towards the clinic over the next 12 months, with IND filings for our anti-tau PRX005 and anti-abeta PRX012 programs, designed to be best-in-class treatments for Alzheimer’s disease. Additionally, our cash position was strengthened by our public offering in March and will be further bolstered when we receive the $60 million milestone earned from Roche. Together this enhances our ability to fund the company through multiple key clinical milestones."

First Quarter and Recent Highlights:

Birtamimab, a potential treatment for AL amyloidosis, is a humanized monoclonal antibody designed to directly neutralize soluble toxic aggregates and promote clearance of amyloid that causes organ dysfunction and failure

Based on the significant survival benefit favoring birtamimab, from the previous VITAL study in a subset of patients categorized as Mayo Stage IV at baseline (HR=0.413, p=0.025, over 9 months), and multiple in-depth discussions with the U.S. Food and Drug Administration (FDA), Prothena announced plans in February 2021 to advance birtamimab into the confirmatory Phase 3 AFFIRM-AL study in Mayo Stage IV patients with AL amyloidosis. AFFIRM-AL is a global, registration-enabling Phase 3 study that will be conducted under a Special Protocol Assessment (SPA) agreement with FDA to enable registration at p≤0.10 for the primary endpoint of all-cause mortality.
Prasinezumab, a potential treatment for Parkinson’s disease, is a humanized monoclonal antibody designed to target a key epitope within the C-terminus of alpha-synuclein and is the focus of the worldwide collaboration with Roche

$60 million milestone earned with first patient dosed in PADOVA study in the second quarter
Two oral presentations by Roche at the 15th International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD 2021) released new data from Part 1 of the Phase 2 PASADENA study. The first presentation highlighted newly presented data from a pre-specified exploratory subgroup analysis showing slowing of clinical decline with prasinezumab was more evident in subgroups with more rapid disease progression. Separately, new digital biomarker data presented from Roche’s remote monitoring technology used in the study was consistent with a potential disease modifying effect of prasinezumab in slowing Parkinson’s disease progression.
PRX004, a potential treatment for ATTR amyloidosis, is a humanized monoclonal antibody designed to deplete the pathogenic, non-native forms of the TTR protein

Oral presentation at the American Academy of Neurology (AAN) 2021 Virtual Meeting featuring results from the Phase 1 study of PRX004 in ATTR amyloidosis. PRX004 showed favorable results as demonstrated by slowing of neuropathy progression for all 7 evaluable patients at 9 months, including improvement in neuropathy in 3 of the 7 patients, and improved cardiac systolic function for all 7 patients. In this Phase 1 study, PRX004 was found to be generally safe and well tolerated across all dose levels.
PRX005, a potential treatment for Alzheimer’s disease (AD), is an investigational antibody that targets tau, a protein implicated in diseases including AD, frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), chronic traumatic encephalopathy (CTE) and other tauopathies.

Oral presentation at AD/PD 2021 highlighting new preclinical data demonstrating that targeting an epitope within the microtubule binding region (MTBR) of tau with PRX005 resulted in superior attributes for the potential treatment of AD. PRX005 demonstrated significant inhibition of cell-to-cell transmission and neuronal internalization in vitro and in vivo, and slowed pathological progression in a tau transgenic mouse model.
Corporate

Appointed Hideki Garren, M.D., Ph.D., as Chief Medical Officer, responsible for leading the clinical and medical organizations to advance Prothena’s clinical pipeline. Dr. Garren joined Prothena after serving as Vice President, Global Head of Neuroimmunology at F. Hoffman-La Roche Ltd. (Roche) & Genentech Inc.
Executed a public offering in March that raised net proceeds of approximately $78 million through the issuance of 4,025,000 ordinary shares
Upcoming Milestones:

Birtamimab

Phase 3 AFFIRM-AL study initiation expected mid-2021
VITAL study 9-month results expected to be presented at a medical conference in 2021
Prasinezumab

Results from Part 2 of the PASADENA study expected to be presented at an upcoming medical conference
PRX004

Phase 2/3 study in patients with ATTR-cardiomyopathy expected to initiate 4Q 2021
PRX005

IND expected by 3Q 2021
$80 million potential payment from Bristol Myers Squibb upon exercising their US license option in 2021
PRX012, a potential treatment for Alzheimer’s disease, is a high affinity monoclonal antibody targeting a key epitope within the N-terminus of Aβ

IND expected by 1Q 2022
Upcoming Investor Conferences

Members of the senior management team will present and participate in investor meetings at the following upcoming investor conferences:

BofA Securities 2021 Virtual Health Care Conference, May 13, 2021, at 8:45 AM ET
RBC Capital Markets Global Healthcare Conference, May 19, 2021 at 8:35 AM ET
Jefferies Virtual Healthcare Conference, June 1, 2021 at 9:00 AM ET
First Quarter 2021 Financial Results and Updated 2021 Financial Guidance

For the first quarter of 2021, Prothena reported a net loss of $36.7 million, as compared to a net loss of $23.6 million for the first quarter of 2020. Net loss per share for the first quarter of 2021 was $0.91, as compared to a net loss per share of $0.59 for the first quarter of 2020.

Prothena reported total revenue of $0.2 million for the first quarter of 2021, from collaboration and license revenue from Roche, as compared to total revenue of $0.1 million for the first quarter of 2020, from collaboration revenue from Roche.

Research and development (R&D) expenses totaled $21.1 million for the first quarter of 2021, as compared to $15.2 million for the first quarter of 2020. The increase in R&D expense for the first quarter of 2021 compared to the same period in the prior year was primarily due to higher R&D consulting expense, higher personnel expense, higher manufacturing expense primarily related to our PRX012 and birtamimab programs, higher clinical trial expense primarily related to birtamimab partially offset by lower PRX004 clinical trial expenses and higher collaboration expense with Roche related to the prasinezumab program. R&D expenses included non-cash share-based compensation expense of $2.0 million for the first quarter of 2021, as compared to $2.0 million for the first quarter of 2020.

General and administrative (G&A) expenses totaled $11.1 million for the first quarter of 2021, as compared to $9.7 million for the first quarter of 2020. The increase in G&A expenses for the first quarter of 2021 compared to the same period in the prior year was primarily related to higher personnel expense and higher expense for our directors and officers insurance premium. G&A expenses included non-cash share-based compensation expense of $4.2 million for the first quarter of 2021, as compared to $3.5 million for the first quarter of 2020.

Total non-cash share-based compensation expense was $6.2 million for the first quarter of 2021, as compared to $5.5 million for the first quarter of 2020.

As of March 31, 2021, Prothena had $345.7 million in cash, cash equivalents and restricted cash (does not include the $60 million milestone earned in the second quarter from Roche) and no debt.

As of May 4, 2021, Prothena had approximately 44.2 million ordinary shares outstanding.

The Company continues to expect the full year 2021 net cash used in operating and investing activities to be $51 to $74 million, which includes receiving the $60 million milestone earned in the second quarter from Roche. The Company is updating its projected year end cash balance to approximately $316 million in cash, cash equivalents and restricted cash (midpoint) (versus prior guidance of $235 million) to include an additional $81 million in net proceeds primarily from the public offering in March. The estimated full year 2021 net cash used in operating and investing activities is primarily driven by an estimated net loss of $79 to $111 million, which includes an estimated $20 million of non-cash share-based compensation expense.