On May 9, 2023 Supernus Pharmaceuticals, Inc. (Nasdaq: SUPN), a biopharmaceutical company focused on developing and commercializing products for the treatment of central nervous system (CNS) diseases, reported financial results for the first quarter of 2023, and associated Company developments (Press release, Supernus, MAY 9, 2023, View Source [SID1234631298]).

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"We are pleased with the strong revenue and earnings performance despite the entry of generic Trokendi XR in the first quarter of 2023," said Jack Khattar, President and CEO of Supernus. "Excluding Trokendi XR, first quarter 2023 net product sales increased 25%, driven by the continued adoption of Qelbree across both pediatric and adult patients and growing demand for GOCOVRI. We remain well-positioned to drive strong revenue and operating earnings growth in 2024 and beyond."

Qelbree Launch Update

Total IQVIA prescriptions were 134,530 in the first quarter of 2023, an increase of 14% compared to total prescriptions of 117,635 in the fourth quarter of 2022. In March 2023, the most recent month available, total prescriptions reached 49,789.
Qelbree continues to expand its base of prescribers, with approximately 19,197 prescribers in the first quarter of 2023, up from 16,822 prescribers from the fourth quarter of 2022.
As previously disclosed, the Company executed a second significant pharmacy benefit manager contract, effective January 2023. We continue making progress in securing and improving managed care coverage.
Product Pipeline Update

SPN-830 (apomorphine infusion device) – Continuous treatment of motor fluctuations ("off" episodes) in Parkinson’s disease (PD)

In April 2023, the Company had a constructive meeting with the U.S. Food and Drug Administration (FDA) to discuss the Complete Response Letter received in October 2022. Based on this meeting, the Company expects to resubmit the New Drug Application for SPN-830 in the fourth quarter of 2023.
SPN-820 – Novel first-in-class activator of mTORC1 for the treatment of treatment-resistant depression

The Phase II multi-center randomized double-blind placebo-controlled parallel design study of SPN-820 in adults with treatment-resistant depression is ongoing. The study will examine the efficacy and safety of SPN-820 over a course of five weeks of treatment in approximately 270 patients. The primary outcome measure is the change from baseline to end of treatment period on the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score, a standard depression rating scale.
SPN-817 – A novel product candidate for the treatment of epilepsy

The open-label Phase II clinical study of SPN-817 in patients with treatment-resistant seizures is ongoing. Depending on the rate of enrollment, the Company expects to have data in the first half of 2024.
R&D Day

Supernus will host an R&D Day in New York City in the Fall of 2023. The management team plans to provide an overview of the Company’s pipeline, including SPN-830, SPN-820, SPN-817 and new clinical candidates from the Company’s discovery program. Further details are forthcoming.
Financial Highlights

Total revenues

For the three months ended March 31, 2023, total revenues were $153.8 million, compared to total revenues of $152.5 million for the same period in 2022. Net product sales were $140.6 million, compared to net product sales of $147.5 million for the same period in 2022. The decrease in net product sales was primarily due to a decrease in net product sales of Trokendi XR, partially offset by an increase in net product sales of both Qelbree and GOCOVRI. Excluding net product sales of Trokendi XR, first quarter 2023 total net product sales increased 25% compared to the same quarter last year.

The following table provides information regarding total revenues during the three months ended March 31, 2023 and 2022 (dollars in millions):

Three Months Ended March 31,
2023 2022 Change %
Net product sales
Trokendi XR $ 34.8 $ 62.8 (45)%
Oxtellar XR 28.9 27.5 5%
GOCOVRI 26.0 22.6 15%
Qelbree 25.8 8.3 **
APOKYN 17.2 18.5 (7)%
Other(1) 7.9 7.8 1%
Total net product sales $ 140.6 $ 147.5 (5)%
Royalty revenues 13.2 5.0 **
Total revenues $ 153.8 $ 152.5 1%
___________________________________________
(1) Includes net product sales of MYOBLOC, XADAGO and Osmolex ER.
** Indicates calculation result is greater than 100%.

Operating earnings (GAAP and non-GAAP)

First quarter 2023 operating earnings (GAAP) was $5.2 million, as compared to operating earnings (GAAP) of $2.0 million for the same period in 2022. The increase was primarily due to growth in net product sales of Qelbree and GOCOVRI and an increase in royalty revenues, partially offset by a decrease in net product sales of Trokendi XR, as well as a decrease in operating expenses.

First quarter 2023 adjusted operating earnings (non-GAAP) were $30.5 million, as compared to $28.0 million for the first quarter of 2022.

Reconciliation of GAAP to Non-GAAP Adjustments

An itemized reconciliation between operating earnings on a GAAP basis and operating earnings on a non-GAAP basis is as follows (dollars in millions):

Three Months Ended
March 31, 2023 Three Months Ended
March 31, 2022
Operating earnings – As Reported (GAAP) $ 5.2 $ 2.0
Adjustments:
Amortization of intangible assets 20.0 20.6
Share-based compensation 6.3 4.0
Contingent consideration expense (gain) (1.6 ) 0.7
Depreciation 0.6 0.7
Operating earnings – As Adjusted (non-GAAP) $ 30.5 $ 28.0
Non-GAAP operating earnings adjusts for non-cash items including amortization of intangible assets, share-based compensation expense, change in fair value of contingent consideration, and depreciation.

Net earnings (GAAP)

First quarter 2023 net earnings (GAAP) and diluted earnings per share (GAAP) were $16.9 million and $0.29, respectively, as compared to $25.6 million, or $0.43, in the same period in 2022.

Balance sheet

At March 31, 2023, the Company’s cash, cash equivalents, restricted cash, current and long-term marketable securities were approximately $686.5 million, compared to $555.2 million as of December 31, 2022. This increase was primarily due to cash generated from operations and the net amount drawn from the line of credit.

On April 1, 2023, the Company paid the total principal amount of $402.5 million due under its 0.625% Convertible Senior Notes due 2023 (2023 Notes), in addition to payment of the remaining outstanding interest due of $1.3 million. Following the repayment, the 2023 Notes are no longer outstanding. The repayment of the 2023 Notes at maturity was financed primarily with available cash on hand and, to a lesser extent, through borrowing under the Company’s existing credit line agreement. The outstanding balance under the credit line as of March 31, 2023 of $78.4 million is expected to be fully repaid by the end of the second quarter 2023.

Full Year 2023 Financial Guidance (GAAP)

For the full year 2023, the Company is increasing prior financial guidance for GAAP operating loss and non-GAAP operating earnings, lowering financial guidance for combined R&D and SG&A expenses, and maintaining its financial guidance for total revenues as set forth below (dollars in millions).

Amount
Total revenues (1) (Includes $60 million to $80 million of Trokendi XR(2)) $580 – $620
Combined R&D and SG&A expenses $450 – $480
Operating loss (3) $(30) – $(10)
___________________________________________
(1) Includes net product sales and royalty revenue.
(2) Reflects generic entry on Trokendi XR in 2023.
(3) Includes amortization of intangible assets and contingent consideration expense (gain).

Full Year 2023 Financial Guidance – GAAP to Non-GAAP Adjustments

An itemized reconciliation between projected operating loss on a GAAP basis and projected operating earnings on a non-GAAP basis is as follows (dollars in millions):

Amount
Operating loss – GAAP $(30) – $(10)
Adjustments:
Amortization of intangible assets $80
Share-based compensation $20 – $24
Contingent consideration $0 – $1
Depreciation $5
Operating earnings – non-GAAP $75 – $100
Non-GAAP Financial Information

This press release contains a financial measure, non-GAAP operating earnings, which does not comply with United States generally accepted accounting principles (GAAP). The non-GAAP financial measure should be considered in addition to, not as a substitute for or in isolation from, or superior to measures prepared in accordance with GAAP. Non-GAAP operating earnings adjusts for non-cash share-based compensation expense, depreciation and amortization, and accretion of contingent consideration, and for factors that are unusual, non-recurring or unpredictable, and excludes those costs, expenses, and other specified items presented in the reconciliation tables in this press release. We believe the use of non-GAAP operating earnings is useful supplemental information to investors regarding the Company’s results of operations and assist management, analysts, and investors in evaluating the performance of the business. There are limitations associated with the use of non-GAAP financial measures. Including such measures may not be entirely comparable to similarly titled measures used by other companies, may not reflect all items of income and expense, as applicable, that affect our operations, potential differences among calculation methodologies, may differ from the non-GAAP information used by other companies, including peer companies, and therefore comparability may be limited. We mitigate these limitations by reconciling the non-GAAP financial measure to the most comparable GAAP financial measure. Investors are encouraged to review the reconciliation. The Company’s 2023 financial guidance is also being provided on both a reported and a non-GAAP basis.

Conference Call Details

Supernus will host a conference call and webcast today, May 9, 2023, at 4:30 p.m. Eastern Time to discuss these results. A live webcast will be available in the Events & Presentations section of the Company’s Investor Relations website www.supernus.com/investors.

Participants may also pre-register any time before the call here. Once registration is completed, participants will be provided a dial-in number with a personalized conference code to access the call. Please dial 15 minutes prior to the start time.

Following the live call, a replay will be available on the Company’s Investor Relations website www.supernus.com/investors. The webcast will be available on the Company’s website for 60 days following the live call.

On May 9, 2023 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a commercial stage biopharmaceutical company focused on novel and targeted oncology therapies, reported its financial results for the three-month period ended March 31, 2023, and provided a corporate update (Press release, Spectrum Pharmaceuticals, MAY 9, 2023, View Source [SID1234631297]).

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First Quarter 2023 and Recent Business Update

Net sales for Q1 2023 totaled $15.6 million, an increase of 54% compared to Q4 2022.
172 targeted accounts purchased ROLVEDON (eflapegrastim-xnst) Injection during the quarter compared to 70 in Q4 2022, an increase of 145%.
Permanent J-Code for ROLVEDON went into effect on April 1, facilitating more efficient and predictable reimbursement in the outpatient setting.
On April 25, announced acquisition by Assertio Holdings, Inc. (Nasdaq: ASRT) ("Assertio"), a specialty pharmaceutical company offering differentiated products to patients, in an all-stock and CVR transaction which is expected to deliver immediate value to stockholders while providing the opportunity to share in future upside of ROLVEDON.
Upfront consideration represents a premium of 65%, and the total potential consideration a premium of 94% to Spectrum’s closing price of $0.69 on April 24, 2023.
Following an anticipated Q3 2023 closing, Assertio stockholders will own approximately 65% of the combined company, and Spectrum stockholders will own approximately 35% of the combined company, on a fully diluted basis.
"Spectrum delivered a strong start to 2023 with outstanding execution in the launch of ROLVEDON. This success is demonstrated through significant quarter-over-quarter sales growth, account expansion, and continued customer receptivity to ROLVEDON’s value proposition," said Tom Riga, President and Chief Executive Officer of Spectrum Pharmaceuticals. "Following the acquisition, we believe the combination of Spectrum’s commercial infrastructure and Assertio’s digital non-personnel resources will set the brand up for long-term success and accelerate the profitability of the combined company."

Financial Results for the Quarter Ended March 31, 2023 (All numbers are from Continuing Operations)

Net sales for the first quarter of 2023 were $15.6 million. During the fourth quarter of 2022 we began to sell our sole commercial product, ROLVEDON, which was approved by the FDA on September 9, 2022. We had no sales during the first quarter of 2022.

Total cost of sales was $1.1 million for the quarter ended March 31, 2023, and consisted primarily of royalties associated with net sales of ROLVEDON, stability testing and packaging costs. This figure did not include any direct costs associated with the manufacture of ROLVEDON, which were previously expensed as research and development expense. As we sell through certain inventory that was expensed prior to FDA approval of ROLVEDON, we expect the cost of sales to remain low through the first nine months of 2023 and to increase thereafter.

Selling, general and administrative expenses for the first quarter of 2023 increased by $4.1 million to $14.0 million as compared to the corresponding prior year period. The increase was due primarily to increased sales and marketing expenses to support the launch of ROLVEDON and an increase in legal and other fees incurred in connection with the pending acquisition by Assertio.

Research and development expenses increased for the three months ended March 31, 2023 by $1.2 million to $5.4 million as compared to the comparable period ended March 31, 2022. The current period had decreased personnel expenses of $5.7 million related to the reduction in workforce during the strategic restructuring that began in January 2022 and decreased program activities of $5.0 million for poziotinib. These period over period decreases were offset by the reversal of an $11.2 million ROLVEDON drug substance accrual during the quarter ended March 31, 2022, which was a concession provided by Hanmi for drug substance which had been accrued during 2021 and is no longer payable.

Net loss from continuing operations was $5.0 million, or $0.02 per basic and diluted share, for the quarter ended March 31, 2023, compared to a net loss of $15.4 million, or $0.09 per basic and diluted share, for the comparable period in 2022.

The Company had a total cash, cash equivalents, and marketable securities balance of approximately $56.1 million as of March 31, 2023.

About ROLVEDON

ROLVEDON (eflapegrastim-xnst) injection is a long-acting granulocyte colony-stimulating factor (G-CSF) with a novel formulation. Spectrum has received an indication to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with clinically significant incidence of febrile neutropenia. ROLVEDON is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation. The BLA for ROLVEDON was supported by data from two similarly designed Phase 3, randomized, open-label, noninferiority clinical trials, ADVANCE and RECOVER, which evaluated the safety and efficacy of ROLVEDON in 643 early-stage breast cancer patients for the treatment of neutropenia due to myelosuppressive chemotherapy. In both studies, ROLVEDON demonstrated the pre-specified hypothesis of non-inferiority (NI) in mean duration of severe neutropenia (DSN) and a similar safety profile to pegfilgrastim. ROLVEDON also demonstrated non-inferiority to pegfilgrastim in the mean DSN across all four cycles (all NI p<0.0001) in both trials.

Please see the Important Safety Information below and the full prescribing information for ROLVEDON at www.rolvedon.com.

Indications and Usage

ROLVEDON is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with clinically significant incidence of febrile neutropenia.

Limitations of Use

ROLVEDON is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Important Safety Information

Contraindications

ROLVEDON is contraindicated in patients with a history of serious allergic reactions to eflapegrastim, pegfilgrastim or filgrastim products. Reactions may include anaphylaxis.
Warnings and Precautions

Splenic Rupture

Splenic rupture, including fatal cases, can occur following the administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) products. Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture.
Acute Respiratory Distress Syndrome (ARDS)

ARDS can occur in patients receiving rhG-CSF products. Evaluate patients who develop fever, lung infiltrates, or respiratory distress. Discontinue ROLVEDON in patients with ARDS.
Serious Allergic Reactions

Serious allergic reactions, including anaphylaxis, can occur in patients receiving rhG-CSF products. Permanently discontinue ROLVEDON in patients who experience serious allergic reactions.
Sickle Cell Crisis in Patients with Sickle Cell Disorders

Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving rhG-CSF products. Discontinue ROLVEDON if sickle cell crisis occurs.
Glomerulonephritis

Glomerulonephritis has occurred in patients receiving rhG-CSF products. The diagnoses were based upon azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy. Generally, events of glomerulonephritis resolved after dose-reduction or discontinuation. Evaluate and consider dose reduction or interruption of ROLVEDON if causality is likely.
Leukocytosis

White blood cell (WBC) counts of 100 x 109/L or greater have been observed in patients receiving rhG-CSF products. Monitor complete blood count (CBC) during ROLVEDON therapy. Discontinue ROLVEDON treatment if WBC count of 100 x 109/L or greater occurs.
Thrombocytopenia

Thrombocytopenia has been reported in patients receiving rhG-CSF products. Monitor platelet counts.
Capillary Leak Syndrome

Capillary leak syndrome has been reported after administration of rhG-CSF products and is characterized by hypotension, hypoalbuminemia, edema and hemoconcentration. Episodes vary in frequency and severity and may be life-threatening if treatment is delayed. If symptoms develop, closely monitor and give standard symptomatic treatment, which may include a need for intensive care.
Potential for Tumor Growth Stimulatory Effects on Malignant Cells

The granulocyte colony-stimulating factor (G-CSF) receptor through which ROLVEDON acts has been found on tumor cell lines. The possibility that ROLVEDON acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which ROLVEDON is not approved, cannot be excluded.
Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) in Patients with Breast and Lung Cancer

MDS and AML have been associated with the use of rhG-CSF products in conjunction with chemotherapy and/or radiotherapy in patients with breast and lung cancer. Monitor patients for signs and symptoms of MDS/AML in these settings.
Aortitis

Aortitis has been reported in patients receiving rhG-CSF products. It may occur as early as the first week after start of therapy. Consider aortitis in patients who develop generalized signs and symptoms such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers (e.g., c-reactive protein and white blood cell count) without known etiology. Discontinue ROLVEDON if aortitis is suspected.
Nuclear Imaging

Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone imaging results.
Adverse Reactions

The most common adverse reactions (≥20%) were fatigue, nausea, diarrhea, bone pain, headache, pyrexia, anemia, rash, myalgia, arthralgia, and back pain.
Permanent discontinuation due to an adverse reaction occurred in 4% of patients who received ROLVEDON. The adverse reaction requiring permanent discontinuation in 3 patients who received ROLVEDON was rash.
To report SUSPECTED ADVERSE REACTIONS, contact Spectrum Pharmaceuticals, Inc. at 1-888-713-0688 or FDA at 1800FDA1088 or www.fda.gov/medwatch

On May 9, 2023 Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, reported the closing of its previously announced public offering of 6,538,500 shares of common stock (or common stock equivalents in lieu thereof) and common warrants to purchase up to 6,538,500 shares of common stock at a combined public offering price of $1.30 (Press release, Soligenix, MAY 9, 2023, View Source [SID1234631296]). The common warrants will have an exercise price of $1.50 per share, will be exercisable immediately and will expire five years from the issuance date. Gross proceeds to Soligenix from this offering are approximately $8,500,000 before deducting commissions and other estimated offering expenses payable by Soligenix.

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A.G.P./Alliance Global Partners acted as the sole placement agent for the offering.

The securities described above were offered pursuant to a registration statement on Form S-1 (File No. 333-271049) previously filed with the Securities and Exchange Commission (SEC) which became effective on May 5, 2023. The offering was made only by means of a prospectus. A copy of the final prospectus relating to the offering may be obtained on the SEC’s website located at View Source Electronic copies of the final prospectus relating to the offering may be obtained from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022, or by telephone at (212) 624-2060, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation, or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On May 9, 2023 Shattuck Labs, Inc. (Shattuck) (NASDAQ: STTK), a clinical-stage biotechnology company pioneering the development of bi-functional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease, reported financial results for the quarter ended March 31, 2023, and provided recent business highlights (Press release, Shattuck Labs, MAY 9, 2023, View Source [SID1234631295]).

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"As a result of steady clinical progress through the first quarter of 2023, key efficacy readouts from our ongoing clinical trials for SL-172154 in PROC and AML/HR-MDS are expected midyear and in the second half of 2023, respectively. Additionally, our poster presentation at ASCO (Free ASCO Whitepaper) next month will provide further context for our selection of 3 mg/kg which we believe to be the optimal dose to move into combination trials with liposomal doxorubicin in patients with PROC. We are further encouraged by ImmunoGen’s positive Phase 3 confirmatory MIRASOL trial last week, and our clinical trial of SL-172154 in combination with mirvetuximab soravtansine is also proceeding nicely," commented Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck. "I am also pleased to report that the dose-escalation portion of our Phase 1 trial in AML/HR-MDS has enrolled very well, and we expect to complete enrollment in that portion of the study in the second quarter. We then plan to proceed immediately to the frontline expansion cohorts in HR-MDS and TP53 mutant AML and to share initial data from those cohorts in the second half of the year. We expect that the data both from the dose-escalation and expansion portions of this trial will help inform what benefit SL-172154 may provide beyond azacitidine alone."

Anticipated Milestones

ARC Platform

SL-172154 (SIRPα-Fc-CD40L)
•Complete data from Phase 1A dose-escalation clinical trial of SL-172154 as monotherapy in PROC to be presented at the 2023 ASCO (Free ASCO Whitepaper) annual meeting
•Initial data from Phase 1B clinical trial of SL-172154 in combination with liposomal doxorubicin in PROC expected midyear 2023
•Complete dose-escalation data, as monotherapy and in combination with azacitidine, for Phase 1A/B clinical trial of SL-172154 in AML and HR-MDS and initial dose-expansion cohort data of SL-172154 in combination with azacitidine in frontline TP53 mutant AML or HR-MDS cohorts expected in the second half of 2023
•Initial data from Phase 1B clinical trial of SL-172154 in combination with mirvetuximab soravtansine in PROC expected in the second half of 2023

GADLEN Platform

GADLEN Preclinical Compounds
•Additional clinical development detail and further program guidance regarding the advancement of potential product candidates from the GADLEN platform expected in 2023
First Quarter 2023 Recent Business Highlights and Other Recent Developments
ARC Clinical-Stage Pipeline
SL-172154 (SIRPα-Fc-CD40L)

•Presenting Complete Dose-Escalation Data from Phase 1A Monotherapy Clinical Trial of SL-172154 in PROC at 2023 ASCO (Free ASCO Whitepaper) Annual Meeting: This open-label, multi-center, dose-escalation clinical trial evaluated the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154 administered intravenously in patients with PROC. Dose escalation reached a maximum administered dose of 10 mg/kg.

•Enrollment Progressing in Ongoing Phase 1A/B Clinical Trial in AML and HR-MDS: This trial is evaluating the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154 as both monotherapy and in combination. In the dose-escalation portion of this trial, enrollment is complete in the monotherapy cohorts through 6 mg/kg, and in the combination cohorts, in combination with azacitidine, through 3 mg/kg. To date, SL-172154, both alone and in combination, has an acceptable safety profile. The final dose-escalation cohort of SL-172154 at 6 mg/kg in combination with azacitidine is expected to complete enrollment in the second quarter. The trial will then evaluate SL-172154 in combination with azacitidine in an expansion cohort in frontline HR-MDS patients and a second expansion cohort in frontline TP53 mutant AML patients. Both expansion cohorts are expected to begin enrollment in the third quarter of 2023, and we now expect to complete enrollment in both expansion cohorts during the second half of 2023. We expect to share full dose-escalation data and initial data from the frontline expansion cohorts in the second half of 2023.

•Enrollment Progressing in Phase 1B Clinical Trial of SL-172154 in Combination with Liposomal Doxorubicin in PROC: Enrollment is continuing in this trial, which is evaluating the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154, using the selected dose of 3 mg/kg, in combination with liposomal doxorubicin in patients with PROC. We expect to present initial data from the trial midyear 2023.

•Dosed First Patients in Phase 1B Clinical Trial of SL-172154 in Combination with Mirvetuximab Soravtansine in PROC: This trial is evaluating the safety, pharmacokinetics, pharmacodynamic effects, and preliminary anti-tumor activity of SL-172154 administered in combination with mirvetuximab soravtansine in patients with PROC. Mirvetuximab soravtansine is an antibody-drug conjugate targeting folate receptor alpha (FRα), which provides for both direct tumor cell killing as well as enhanced macrophage phagocytosis through binding with Fc gamma receptors and has received accelerated approval for PROC patients whose tumors are shown to be FRα positive, defined as ≥75%, as determined by the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay. Preclinical studies have shown that both of these killing mechanisms are complementary to the mechanism of SL-172154 by enhancing the activity of macrophages to phagocytose FRα- expressing ovarian cancer cells, and that SL-172154 may broaden the activity of mirvetuximab, particularly in patients with tumors that express lower levels of FRα. We intend to enroll patients with broader FRα expression, including those with "high" (greater than ≥75%), "medium" (≥50% to <75%), and "low" (≥25% to <50%) expression of FRα, as determined by the VENTANA FOLR1 (FOLR1-2.1). We expect to present initial data from the trial in the second half of 2023.
Gamma Delta T Cell Engager (GADLEN) Preclinical Pipeline

Preclinical Pipeline Development

•We presented preclinical data from GADLEN platform at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in April 2023 that demonstrated that the CD20-targeted GADLEN efficiently directs small numbers of human Vγ9Vδ2 T cells to serially kill greater than 99% of human B cells in a humanized mouse model. These results led to the first study of a GADLEN compound in non-human primates, where once again treatment with a CD20-targeted GADLEN directed low frequencies of endogenous Vγ9Vδ2 T cells to eliminate CD20 positive B cells with a rapid kinetic. The GADLEN compound was well tolerated in non-human primates up to the highest administered dose of 25 mg/kg, without evidence of cytokine release syndrome or other toxicities, potentially providing differentiation from CD3-directed T cell engagers.

First-Quarter 2023 Financial Results

•Cash and Cash Equivalents and Investments: As of March 31, 2023, cash and cash equivalents and investments were $135.5 million, as compared to $239.2 million as of March 31, 2022.
•Research and Development (R&D) Expenses: R&D expenses were $16.7 million for the quarter ended March 31, 2023, as compared to $19.2 million for the quarter ended March 31, 2022. This decrease was primarily driven by a decrease in expense associated with the manufacture of clinical trial materials to support our ongoing clinical trials.
•General and Administrative (G&A) Expenses: G&A expenses were $5.1 million for the quarter ended March 31, 2023, as compared to $5.0 million for the quarter ended March 31, 2022.
•Net Loss: Net loss was $20.7 million for the quarter ended March 31, 2023, or $0.49 per basic and diluted share, as compared to a net loss of $24.5 million for the quarter ended March 31, 2022, or $0.58 per basic and diluted share.

2023 Financial Guidance

Shattuck believes its cash and cash equivalents and investments will be sufficient to fund its operations through year-end 2024, beyond results from its Phase 1 clinical trials of SL-172154. This cash runway guidance is based on the Company’s current operational plans and excludes any additional capital that may be received, proceeds from business development transactions, and/or additional costs associated with clinical development activities that may be undertaken.

About SL-172154

SL-172154 (SIRPα-Fc-CD40L) is an investigational ARC fusion protein designed to simultaneously inhibit the CD47/SIRPα checkpoint interaction and activate the CD40 costimulatory receptor to bolster an anti-tumor immune response in patients with advanced cancer. Multiple Phase 1 clinical trials are ongoing for patients with PROC (NCT04406623, NCT05483933) and patients with AML and HR-MDS (NCT05275439).

On May 9, 2023 Seres Therapeutics, Inc. (Nasdaq: MCRB), a leading microbiome therapeutics company, reported its first quarter 2023 financial results and provided business updates (Press release, Seres Therapeutics, MAY 9, 2023, View Source [SID1234631294]).

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"We were thrilled to recently announce the FDA approval of VOWST, the first and only FDA-approved orally administered microbiota-based therapeutic, and with the favorable label indication received from the FDA. Adult recurrent C. difficile infection patients who could benefit from using VOWST, per the label, can access it, including those with first recurrence. The approval of VOWST marks Seres’ transformation to a commercial organization and provides definitive validation of the promise of our microbiome technology platform," said Eric Shaff, President and Chief Executive Officer at Seres. "We are looking forward to launching VOWST in the United States in June alongside our collaborator, Nestlé Health Science.

"We also continue to advance our earlier-stage pipeline, including SER-155, designed to prevent infections and/or graft-versus-host disease in patients undergoing allogeneic hematopoietic stem cell transplant, or allo-HSCT. We are also very pleased to report today new Phase 1b data from study Cohort 1 that support our therapeutic objective of reducing serious enteric infections, resulting bloodstream infections and GvHD. These encouraging initial data support the continued development in the ongoing placebo-controlled study Cohort 2.

"Finally, we have substantially strengthened our balance sheet and expect to further enhance our cash position with the receipt of a $125 million milestone payment from Nestlé based on the FDA approval."

First Quarter and Recent Program and Corporate Updates

FDA Approval of VOWST: In April 2023, Seres and Nestlé Health Science announced the Food and Drug Administration (FDA) approval of VOWST (fecal microbiota spores, live-brpk), formerly called SER-109, an orally administered microbiota-based therapeutic to prevent recurrence of C. difficile Infection (CDI) in adults following antibacterial treatment for recurrent CDI (rCDI). VOWST is thought to facilitate restoration of the gut microbiome. The Company anticipates VOWST product availability and launch in June.

The FDA approval of VOWST was supported by a robust Phase 3 development program that included the ECOSPOR III and ECOSPOR IV studies. VOWST was previously granted Breakthrough Therapy and Orphan Drug Designations by the FDA.

ECOSPOR III was a multicenter, randomized, placebo-controlled study in individuals with rCDI, the results of which were published in the New England Journal of Medicine. The study’s primary objective was to demonstrate the reduction of CDI recurrence with VOWST. In ECOSPOR III, VOWST was shown to reduce CDI recurrence at eight weeks, with approximately 88% of individuals recurrence-free at eight weeks post-treatment, compared to 60% in participants who received placebo. In addition, at six months post-treatment, 79% of the VOWST group were demonstrated to be recurrence-free, compared to 53% in the placebo group. No treatment-related serious adverse events were observed in the active arm and the frequency of treatment-related adverse events was similar between the VOWST and placebo arms. The most common adverse reactions through eight weeks in VOWST treated participants versus placebo were solicited events of abdominal distention (31.1% VOWST versus 29.3% placebo), fatigue (22.2% VOWST versus 21.7% placebo), constipation (14.4% VOWST versus 10.9% placebo), chills (11.1% versus 7.6% placebo), and unsolicited event of diarrhea (10.0% versus 4.3% placebo).

ECOSPOR IV was an open-label, single arm study evaluating VOWST in 263 adult participants with rCDI. Study results were published in the JAMA Network Open. The ECOSPOR IV study results contributed to the VOWST safety database and supported product approval.

Seres and Nestlé Health Science are committed to helping appropriate patients who have been prescribed VOWST obtain access. Additional details about VOWST access programs will be available at launch. Please see vowst.com for further information.

In July 2021, Seres and Nestlé Health Science entered into an agreement to jointly commercialize VOWST in the U.S. and Canada. Nestlé Health Science is leveraging its global pharmaceutical business and assuming the role of lead commercialization party, including the utilization of its existing infrastructure, 150-person gastrointestinal sales force, payer access team and a recently hired 20-person hospital salesforce.

New SER-155 Phase 1b Cohort 1 Study Results: In a separate press release issued today, Seres announced new safety and pharmacology study data including:

•
favorable tolerability profile observed, with no serious adverse events attributed to SER-155 administration;

•
bacteria in the SER-155 consortia engrafted into the gastrointestinal (GI) microbiome, with a magnitude and kinetics consistent with expectation from prior clinical results from other Seres microbiome therapeutics; and

•
cumulative incidence of domination with ESKAPE pathogen families was rare and observed at substantially lower incidence rates than observed in a reference population of allo-HSCT patients.1

SER-155 is an investigational, oral, 16 strain, cultivated microbiome therapeutic designed to prevent colonization and reduce the abundance of ESKAPE pathogens (e.g., from families such as Enterococcaceae, Enterobacteriaceae, Streptococcaceae, Staphylococcaceae) in the GI tract to reduce the risk of enteric driven bloodstream infections and other downstream consequences such as GvHD in patients receiving allo-HSCT. SER-155 has the potential to also impact antimicrobial resistance (AMR), including infections caused by carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant Enterococci (VRE). The development of SER-155 is supported by SER-109 Phase 3 ECOSPOR III study exploratory results showing the decolonization of gut pathogens, including bacterial carrying antibiotic resistance genes, in the GI microbiome following SER-109 administration.

The ongoing SER-155 Phase 1b study includes two cohorts with Cohort 1 designed to assess safety and drug pharmacology, including the engraftment of drug bacteria in the gastrointestinal tract.

Enrollment of the Cohort 2 study is ongoing, incorporating a randomized, double-blinded placebo-controlled design to further evaluate safety and engraftment, as well as clinical outcomes, and will enroll approximately 60 subjects administered either SER-155 or placebo at a 1:1 ratio. The Company anticipates obtaining Cohort 2 study data in mid-2024.

Infection Protection research: The Company continues to conduct research to bring forward new microbiome therapeutics as a novel approach for Infection Protection for medically compromised individuals, including those with cancer neutropenia, cirrhosis or solid organ transplant. Preclinical studies are evaluating the potential to reduce the abundance of targeted pathogens to decrease the potential for pathogen transmission, strengthen epithelial barriers to further reduce translocation and the frequency of bloodstream infections, and to modulate immune responses to tackle medical complications such as graft-versus-host disease (GvHD). The Company plans to announce an additional Infection Protection clinical development program in 2023.

Ulcerative Colitis (UC) research: The Company previously reported clinical, microbiome and metabolomic data from the SER-287 Phase 2b study and the first cohort of its SER-301 Phase 1b study. Available data for these investigational microbiome therapeutics suggest that there may be an opportunity to utilize biomarker-based patient selection and stratification for future studies. Research activities remain ongoing to inform potential further development activities.

Financial Results

Seres reported a net loss of $71.2 million for the first quarter of 2023, as compared with a net loss of $56.6 million for the same period in 2022.

Research and development expenses for the first quarter of 2023 were $44.0 million, compared with $39.6 million for the same period in 2022. The research and development expenses were primarily related to Seres’ VOWST clinical development program and manufacturing costs, as well as personnel expenses. Included in the first quarter 2023 R&D expenses of $44 million is approximately $16 million of commercial manufacturing costs for VOWST. Following the approval of VOWST, R&D expenses in the P&L will no longer include VOWST commercial manufacturing costs, as these costs will be capitalized and recognized on Seres’ balance sheet.

General and administrative expenses for the first quarter of 2023 were $22.5 million, compared with $18.6 million for the same period in 2022. General and administrative expenses were primarily related to personnel expenses, professional fees, including VOWST commercial readiness and pre-launch expenses, and facility costs.

The Company has expanded its capabilities across the organization in support of VOWST approval and launch and is focused on driving operational efficiencies and pursuing opportunities to optimize its cost structure.

Seres ended the first quarter of 2023 with $106.5 million in cash, cash equivalents and investments as compared with $181.3 million at the end of 2022.

In April 2023, Seres announced that it had entered into a new $250 million senior secured debt facility provided by funds managed by Oaktree Capital Management, L.P. The Company drew the first tranche of $110 million at closing, with three additional tranches available. These additional tranches include $90 million that will be available in two tranches of $45 million each based upon the achievement of certain applicable VOWST sales targets, and an additional $50 million will be available to the Company at Oaktree’s discretion to support potential future business development activities. Of the $110 million advanced by Oaktree at closing, approximately $53 million retires outstanding debt, and after deducting fees and expenses, the net proceeds to the Company were approximately $50 million.

Seres is also due to receive a $125 million milestone payment from Nestlé Health Science associated with the FDA approval of VOWST. The Company also anticipates the receipt of proceeds from the supply of VOWST initial inventory to Nestlé.

Seres pro-forma cash balance as of March 31, 2023, is approximately $282 million, including the VOWST approval milestone and the net proceeds from its debt financing with Oaktree.

Conference Call Information

Seres’ management will host a conference call today, May 9, 2023, at 8:30 a.m. ET. To access the conference call, please dial 800-715-9871 (domestic) or 646-307-1963 (international) and reference Conference ID 5098595. To join the live webcast, please visit the "Investors and News" section of the Seres website at www.serestherapeutics.com.

A webcast replay will be available on the Seres website beginning approximately two hours after the event and will be archived for at least 21 days.

INDICATION AND IMPORTANT SAFETY INFORMATION FOR VOWST

INDICATION

VOWST is indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in individuals 18 years of age and older following antibacterial treatment for recurrent CDI (rCDI).

Limitation of Use: VOWST is not indicated for treatment of CDI.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Transmissible infectious agents: Because VOWST is manufactured from human fecal matter, it may carry a risk of transmitting infectious agents. Report any infection that is suspected to have been transmitted by VOWST to Aimmune Therapeutics, Inc. at 1-833-246-2566.

Potential presence of food allergens: VOWST may contain food allergens. The potential to cause adverse reactions due to food allergens is unknown.

ADVERSE REACTIONS

The most common adverse reactions (reported in ≥5% of participants) were abdominal distension (31.1%), fatigue (22.2%), constipation (14.4%), chills (11.1%), and diarrhea (10.0%).

To report SUSPECTED ADVERSE REACTIONS, contact Aimmune Therapeutics at 1-833-AIM-2KNO (1-833-246-2566), or the FDA at 1-800-FDA-1088, or visit www.fda.gov/MedWatch.

DRUG INTERACTIONS

Do not administer antibacterials concurrently with VOWST.

Please see Full Prescribing Information and Patient Information