On November 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 the presentation of preclinical data for APVO603, the Company’s bispecific antibody targeting 4-1BB (CD137) and OX40 (CD134), at the Society for Immunology in Cancers (SITC) (Free SITC Whitepaper) 2021 Annual Meeting (Press release, Aptevo Therapeutics, NOV 11, 2021, View Source [SID1234595288]).

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Poster #795 entitled, "APVO603: A dual 4-1BB and OX40 bispecific approach utilizing ADAPTIR technology designed to deliver a conditional T cell/NK response against solid tumors," will be presented and displayed on-site on Saturday, November 13th in Washington, D.C. Data in the poster showed that APVO603 enhanced dose-dependent control of in vitro tumor cell lysis when paired with a bispecific T-cell engager when compared either alone. Of note, investigators show that APVO603 has minimal impact on regulatory T cell suppression of CD8+ T cells’ proliferation in vitro.

"APVO603 is a differentiated bispecific antibody with the potential to leverage the benefits of 4-1BB and OX40 in a single agent. Further, the tethering of molecules has the potential to reduce safety risks and improve potency profiles by targeting responses specifically to sites of active inflammation and limiting on-target toxicity," said Hilario Ramos, Senior Director of Immunobiology at Aptevo. "In addition, the data presented here demonstrate that this combination has the potential to promote anti-tumor responses two-fold. First, by improving the fitness of exhausted effector CD8+ T cells. Second, by reducing the potential for activation of suppressive responses by T regulatory subsets. This dual biological mechanism of action offers the potential for development of a compound that acts against both solid and hematologic tumors and in the presence of addition immunomodulatory treatments or modalities such as CAR T or adoptive immune cell therapies."

Aptevo CEO Marvin White commented, "We are very encouraged by the results reported in this poster, and we are excited to continue to develop APVO603 and provide this update on our progress as we work to advance the compound."

Title: APVO603: A dual 4-1BB and OX40 bispecific approach utilizing ADAPTIRTM technology designed to deliver a conditional T cell/NK response against solid tumors
Presenter: Hilario Ramos, Senior Director of Immunobiology at Aptevo
Date/Time: Saturday, November 13, 2021

About APVO603

APVO603 is a dual agonist bispecific antibody employing a novel mechanism of action to simultaneously target 4-1BB (CD137) and OX40 (CD134), both members of the TNF Receptor Superfamily. Dual targeting of 4-1BB and OX40 provides synergistic co-stimulation of T cells with the potential to amplify the cytotoxic function of activated T cells and NK cells, potentially leading to more robust anti-tumor responses.

On November 11, 2021 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in cell therapy to treat cancer, reported that it will report updated clinical and translational data from its pivotal SPEARHEAD-1 trial with afamitresgene autoleucel (afami-cel, formerly ADP-A2M4) in patients with advanced synovial sarcoma or myxoid/round cell liposarcoma (MRCLS) at the Connective Tissue Oncology Society (CTOS) annual meeting (Press release, Adaptimmune, NOV 11, 2021, View Source [SID1234595287]).

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"The positive results presented at CTOS further validate the potential of this therapy to address a great unmet medical need for patients with synovial sarcoma and MRCLS," said Elliot Norry, Adaptimmune’s Chief Medical Officer. "We are confident that these data will support our BLA filing for afami-cel next year."

"Afami-cel would provide a new treatment option for patients with synovial sarcoma, offering benefits that we have rarely seen with therapies currently available for this patient population," said Dr. Brian A. Van Tine, Professor of Medicine and of Pediatrics at Washington University School of Medicine in St. Louis. "This is a game changer for patients with a high unmet medical need."

Clinical data will be presented in an oral presentation by Dr. Brian Van Tine of the Washington University School of Medicine in St. Louis (Abstract #1080870) during the Immunotherapy & Immune Microenvironment Session starting at 10:00 a.m. EST on November 12th.

Preliminary translational insights from the Phase 2 SPEARHEAD-1 trial will also be presented in a poster (Abstract #1080366) by Dr. Sandra P. D’Angelo of Memorial Sloan Kettering Cancer Center during the Immunology & Immunotherapy Session beginning at 2:30 p.m. EST on November 12th.

Efficacy data validate the meaningful clinical benefit of afami-cel (data cut-off September 1, 2021)

50 patients had received afami-cel (42 with synovial sarcoma, 8 with MRCLS)
Median age of patients was 41 years (range: 19 to 73) and they had received a median of three prior lines of therapy (range: 1 to 12)
The median dose was 8.5 billion transduced SPEAR T-cells (range: 2.7 to 10)
Three patients had scans awaiting Independent Review and 47 patients were evaluable
The primary endpoint for SPEARHEAD-1 is response according to RECIST v1.1 evaluated by Independent Review 1
Based on the reported overall response rate, the trial will meet its primary endpoint in the final analysis planned later this year
Per Independent Review, the overall response rate was 34% (16/47 patients with partial responses [PRs])
The overall response rate was 36% in patients with synovial sarcoma, and 25% for patients with MRCLS
The disease control rate (defined as stable disease, PR, or CR) was 85% per Independent Review
The overall response rate and disease control rate per Independent Review were comparable to the assessments by Investigator Review (34% and 84%, respectively)
Durability is encouraging and the median duration of response has not been reached
75% of patients with response remain ongoing and the duration ranged from 4.3+ to 65.3+ weeks
Afami-cel was well-tolerated and has a favorable benefit:risk profile as of data cut-off

Thirty-three (66%) patients experienced adverse events of cytokine release syndrome (CRS), most of which were lower grade: Grade 1 or 2 (n=32); Grade 3 (n=1)
The most common serious adverse event (SAE) of any grade was CRS reported in 6% of patients
Eight (16%) patients experienced ≥ Grade 3 cytopenia at Week 4

Emerging translational data support clinical benefit seen in patients with afami-cel

Afami-cel SPEAR T-cells successfully engrafted in all patients and maintained high levels of persistence in most patients followed for at least 6 months post-infusion
CD8+ SPEAR T-cells in drug products administered killed >70% tumor cells in vitro
Serum cytokine response profile indicates an IFNγ-driven mechanism of action, signaling an afami-cel induced immune response
Clinical benefit seen across a broad range of MAGE-A4 expression
Post-infusion biopsies indicated that infiltrating afami-cel SPEAR T-cells co-localize with tumor and additional immune cells, with evidence of activated and proliferative state and adaptive-immune response
Conclusion from the Phase 2 SPEARHEAD-1 trial

The trial will meet its primary endpoint for efficacy for this pivotal trial
As of September 1, 2021, overall response rate was 34% with a disease control rate of 85% per Independent Review in 47 heavily pre-treated patients
Durability of responses is encouraging, and the median duration of response has not been reached
The benefit:risk profile of afami-cel has been favorable, with mainly low-grade CRS and tolerable/reversible hematologic toxicities
Translational data confirm that afami-cel is active against MAGE-A4 expressing targets both in vitro and in vivo
These data will be used to support Adaptimmune’s Biologics License Application (BLA) submission next year
Overview of SPEARHEAD-1 trial design
SPEARHEAD-1 is a Phase 2, open-label trial for people with advanced synovial sarcoma or MRCLS to evaluate the efficacy, safety, and tolerability of afami-cel. Afami-cel SPEAR T-cells target MAGE-A4+ tumors. MAGE-A4 is highly expressed in synovial sarcoma and MRCLS in the context of HLA-A*02. Compelling clinical responses in patients with synovial sarcoma were previously reported with afami-cel in a Phase 1 trial (CTOS 2020).

Approximately 90 patients are planned to be treated: 45 in Cohort 1 and 45 in Cohort 2. Enrollment in Cohort 1 is complete, and Cohort 2 is currently recruiting. The primary efficacy analysis will be for Cohort 1 only, which will be used to support the BLA filing next year. No formal hypothesis testing is planned for Cohort 2. Cohort 2 will strengthen the efficacy and safety database and will aid in descriptive sub-group analyses.

Key eligibility criteria: ECOG performance status of 0 or 1; HLA*02 positive with MAGE-A4 expression in ≥ 30% of tumor cells ≥ 2+ by immunohistochemistry; aged ≥ 16 and ≤ 75 years; and patients must have received either an anthracycline- or ifosfamide-containing regimen. Eligible patients received afami-cel doses between 1–10 × 109 transduced T-cells after receiving lymphodepleting chemotherapy.

On November 11, 2021 Knight Therapeutics Inc. (TSX: GUD) ("Knight" or "the Company"), a leading Pan-American (ex-US) specialty pharmaceutical company, reported financial results for its third quarter ended September 30, 2021 (Press release, Knight Therapeutics, NOV 11, 2021, View Source [SID1234595285]). All currency amounts are in thousands except for share and per share amounts. All currencies are Canadian unless otherwise specified.

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Q3 2021 Highlights

Financials

Revenues were $73,340, an increase of $28,101 or 62% over the same period in prior year.
Gross margin of $37,766 or 51% compared to $19,533 or 43% in the same period in prior year.
Adjusted EBITDA1 was $17,334, an increase of $13,118 or 311% over the same period in prior year.
Net loss on financial assets measured at fair value through profit or loss of $21,301 for the three-month period ended September 30, 2021.
Net gain on financial assets measured at fair value through profit or loss of $16,644 for the nine-month period ended September 30, 2021.
Net loss was $8,586, compared to $17,492 net income in the same period in prior year.
Cash inflow from operations was $10,321, compared to a cash outflow from operations of $8,412 in prior year.
Corporate Developments

Re-launched a normal course issuer bid ("NCIB") in July 2021 and purchased 2,963,022 common shares for an aggregate cash consideration of $15,361.
Hired Monica Percario as Global VP Scientific Affairs, Daniela Marino as Global VP Legal and Compliance and Susan Emblem as Global VP Human Resources.
Products

Entered into exclusive supply and distribution agreement with Incyte Biosciences International Sàrl ("Incyte") for tafasitamab and pemigatinib in Latin America
Strategic Investments

Received distributions of $2,042 from strategic fund investments and realized a gain of $1,634.
Key Subsequent Events

Received $9,243 (US$7,460) as part of the final distribution from the liquidation of New Emerging Medical Opportunities Fund II Ltd.
Re-financed Bancolombia loan extending the maturity date from December 14, 2021 to October 26, 2026.
Purchased an additional 1,009,725 common shares through NCIB for an aggregate cash consideration of $5,258.
"I am excited to announce that for a second consecutive quarter, Knight achieved record quarterly results despite the ongoing challenges posed by the pandemic. During the last 9 months we executed on multiple fronts with our business development team closing Exelon, entering into an exclusive supply and distribution agreement with Incyte while the commercial team continuing to deliver on strong growth of our key brands and the operational teams executing on integration and systems implementation. Furthermore, we strengthened Knight’s management team by adding a Global VP Scientific Affairs, a Global VP Legal and Compliance and a Global VP Human Resources, to continue delivering on growth and operational excellence," said Samira Sakhia, President and Chief Executive Officer of Knight Therapeutics Inc.

__________________________________________________________________________________

1 Adjusted EBITDA is not a defined term under IFRS, refer to the definitions below for additional details.

Revenue: For the quarter ended September 30, 2021 revenues increased by $28,101 or 62% compared to the same prior year period. On a constant currency basis, revenues increased by $27,378 or 62%. The growth in revenues on a constant currency basis is explained as following:

An estimated increase in revenues of approximately $9,200 to $11,500 driven by the increased demand of certain of our infectious diseases products to treat invasive fungal infections associated with COVID-19. Of this amount, Knight estimates approximately $3,200 to $4,200 was not utilized during the quarter.
An increase in revenues of $9,905 driven by the acquisition of Exelon.
An increase in revenues of $6,047 or 76%, from $7,918 to $13,965, driven by the growth of our recently launched products, including Cresemba, Lenvima, Halaven, Nerlynx, Trelstar and certain BGx products.
Gross margin: For the quarter ended September 30, 2021 gross margin increased from 43% to 51% explained by a change in product mix, lower inventory provision recorded in Q3-21 compared to Q3-20 offset by the re-negotiation of certain license agreements and the depreciation of the LATAM currencies. The gross margin would have been 54%, an increase of 3%, from 51% after excluding the adjustment of hyperinflation accounting in accordance with IAS 29.

Selling and marketing: For the quarter ended September 30, 2021, selling and marketing increased by $2,227 or 29% and on a constant currency basis by $2,165 or 29% as compared to the same prior year period. Excluding, the allowance for expected credit losses, S&M increased by $1,857 or 25% due to increase in certain variable costs such as distribution and compensation as well as an increase in selling and marketing activities related to product launches and Exelon.

General and administrative: For the quarter ended September 30, 2021, general and administrative expenses decreased by $2,072 or 19% and on a constant currency basis by $1,814 or 18% as compared to the same period in prior year. Excluding the non-recurring costs incurred in Q3-20 related to the Unified Tender Offer of $3,490, G&A increased by $1,676 or 17%. The increase is driven by an increase in the variable compensation and certain professional fees.

Amortization of intangible assets: For the quarter ended September 30, 2021, amortization of intangible assets increased by $5,496, or 96%, mainly explained by the amortization of Exelon acquired during Q2-21 partially offset by the depreciation of LATAM currencies.

Interest income: Interest income is the sum of interest income on financial instruments measured at amortized cost and other interest income. For the quarter ended September 30, 2021, interest income was $1,402, a decrease of $1,786 or 56%, compared to the same prior year period, due to a decrease in interest rates, the average cash and marketable securities balances and a lower average loan balance.

Interest expense: The interest expense relates to interest incurred on bank loans. For the quarter ended September 30, 2021 interest expenses was $959, an increase of $137 or 17% compared to the same period in the prior year due to higher interest rates.

Adjusted EBITDA: For the quarter ended September 30, 2021 adjusted EBITDA increased by $13,118 or 311% and on a constant currency basis by $13,637 or 369%, compared to Q3-20. The growth in adjusted EBITDA is driven by an increase in gross of margin of $17,901 offset by an increase in operating expenses adjusted for acquisition and transaction costs as well as non-recurring expenses.

Net loss or income: For the quarter ended September 30, 2021, net loss was $8,586 compared to net income of $17,492 for the same period last year. The variance mainly resulted from the above-mentioned items as well as a net loss on the revaluation of financial assets measured at fair value through profit or loss of $21,301 in the third quarter of 2021 versus a net gain of $12,873 in the prior year period mainly due to unrealized losses and gains on revaluation of the strategic fund investments.

Cash, cash equivalents and marketable securities: As at September 30, 2021, Knight had $156,029 in cash, cash equivalents and marketable securities, a decrease of $236,196 or 60% as compared to December 31, 2020. The variance is primarily due to cash outflows related to the acquisition of Exelon, the shares repurchased through NCIB and the repayments of bank loans offset by cash generated from operating activities.

Financial assets: As at September 30, 2021, financial assets were at $189,743, a decrease of $4,212 or 2%, as compared to the prior period, mainly due to an increase of $17,063 due to mark-to-market adjustments offset by decrease of 16,652 due to net distributions in Knight’s fund investments, loan repayments of $2,494 and disposal of equity investments of $2,624 during the period. Given the nature of the fund investments there could be significant fluctuations in the fair value of the underlying assets. During the quarter ended September 30, 2021, the Company recorded an unrealized loss of $20,629, as a result of the share price decrease of Singular Genomics Systems, Inc. ("SGS"), an investment held within Domain Associated LLC. Should the share price of SGS remain at this level, the Company would record a life to date unrealized gain of approximately $12,929 [USD 10,550] on this investment.

Bank Loans: As at September 30, 2021, bank loans were at $36,328, a decrease of $15,442 or 30% as compared to the prior period, mainly due to loan repayment of $14,911.

Product Updates

On September 22, 2021, Knight entered into a definitive agreement with Incyte Biosciences International Sàrl, for the exclusive rights to distribute tafasitamab (sold as Monjuvi in the United States and Minjuvi in Europe) and pemigatinib (Pemazyre) in Latin America. Under the terms of the agreement Knight will be responsible for seeking the necessary regulatory approvals and distributing both products in Latin America.

Knight expects to submit tafasitamab and pemigatinib in key LATAM countries in the second half of 2022.

NCIB

During the three-month and nine-month periods ended September 30, 2021, the Company purchased 2,963,022 and 7,844,438 common shares for $15,361 and $40,907, respectively.

Subsequent to quarter-end, the Company purchased an additional 1,009,725 common shares for an aggregate cash consideration of $5,258.

Conference Call Notice

Knight will host a conference call and audio webcast to discuss its third quarter results today at 8:30 am ET. Knight cordially invites all interested parties to participate in this call.

On November 11, 2021 Verastem Oncology (Nasdaq:VSTM), a biopharmaceutical company committed to advancing new medicines for patients battling cancer, reported that the Company will present at the Jefferies London Healthcare Conference (Press release, Verastem, NOV 11, 2021, View Source [SID1234595284]). The presentation will be made available for on-demand listening beginning Thursday, November 18, 2021 at 8:00 a.m. GMT (3:00 a.m. ET).

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A webcast of the presentation will be available on investors section of the Company’s website at www.verastem.com. An archived presentation will be made available for 30 days.

On November 11, 2021 MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number: 4875), reported that Grazia Ambrosini, PhD, an associate research scientist at Columbia University Vagelos College of Physicians and Surgeons, presented data regarding MN-166 (ibudilast) in a uveal melanoma (UM) model study at the 10th Annual CURE OM Global Science Meeting held online as a part of the Society for Melanoma Research International Congress on October 28, 2021 (Press release, MediciNova, NOV 11, 2021, View Source [SID1234595283]).

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This study was a collaborative effort between MediciNova and Dr. Ambrosini, Richard D. Carvajal, MD, associate professor of medicine at Columbia Vagelos College of Physicians and Surgeons and co-director of the Precision Oncology and Systems Biology research program at the Herbert Irving Comprehensive Cancer Center (HICCC), and Gary Schwartz, MD, professor of oncology at Vagelos College of Physicians and Surgeons, Division Chief of Hematology/Oncology at Columbia University Irving Medical Center, and Deputy Director at the HICCC.

The highlights of Dr. Ambrosini’s presentation are follows:

The role of UM exosomes in the crosstalk with hepatic cells was investigated in co-culture migration assays and in a mouse metastatic model.
UM exosomes induce activation of cell signaling pathways and the release of cytokines and growth factors from hepatocytes. The exosome-stimulated hepatocyte conditioned media (HCM) could in turn induce migration of UM cells.
Macrophage migration inhibitory factor (MIF) was the major player in these mechanisms and its blockade inhibited cell migration in co-cultures with exosome-stimulated hepatocytes and prevented the development of metastases in vivo.
MN-166 reduced migrated UM cell count in UM-exosome-stimulated HCM (p<0.001).
Quantified bioluminescence intensity for each animal in the abdominal region was significantly reduced by MN-166 treatment in the UM mouse model (p<0.05).
MN-166 prevented metastasis in a mouse UM metastasis model.
Dr. Carvajal commented, "We are excited about the preclinical data generated with the MIF inhibitor MN-166 in this uveal melanoma model study. Uveal melanoma is the most common primary intraocular malignancy and nearly half of patients ultimately will develop metastasis. Metastases are most frequently localized to the liver and associated with a poor prognosis. Currently there are no effective preventive treatments for uveal melanoma. Previously, our group identified MIF as a critical mediator of metastatic spread. In our new study, MN-166 treatment prevented remote metastasis in the orthotopic uveal melanoma model."

Kazuko Matsuda, M.D. Ph.D, MPH., Chief Medical Officer, MediciNova, Inc., commented, "In clinical practice, cancer metastasis is often the major driver of cancer-related death rather than the primary cancer. We are very excited about MN-166’s potential to prevent metastasis in uveal melanoma. We previously reported that MN-166 reduced levels of immune suppressive myeloid-derived suppressor cells (MDSCs) and enhanced CD8 T cell activity in the tumor microenvironment. The new data from this UM model study suggested that treatment with MN-166 can potentially address significant unmet medical needs for novel and effective therapies for patients with UM at risk of metastasis. We are looking forward to moving to a clinical trial and we are optimistic that this project could help patients with uveal melanoma and other malignancies."

About MN-166 (ibudilast)

MN-166 (ibudilast) is a small molecule compound that inhibits phosphodiesterase type-4 (PDE4) and inflammatory cytokines, including macrophage migration inhibitory factor (MIF). It is in late-stage clinical development for the treatment of neurodegenerative diseases including ALS, progressive MS (multiple sclerosis), and DCM (degenerative cervical myelopathy); glioblastoma, CIPN (chemotherapy-induced peripheral neuropathy), and substance use disorder. In addition, MN-166 (ibudilast) is being evaluated in patients at risk for developing acute respiratory distress syndrome (ARDS).