On February 4, 2021 Biogen Inc. ("Biogen") (Nasdaq: BIIB) reported the commencement of a private offer to exchange (the "Exchange Offer") any and all of its outstanding 5.200% Senior Notes due 2045 (the "Old Notes"), totaling $1.75 billion in aggregate principal amount, for a new series of senior notes to be issued by Biogen (the "New Notes") and cash, if any, on the terms and conditions set forth in the Offering Memorandum dated February 4, 2021 (the "Offering Memorandum") and the accompanying eligibility letter (the "Eligibility Letter"), Canadian beneficial holder form and notice of guaranteed delivery (collectively, the "Exchange Offer Documents") (Press release, Biogen, FEB 4, 2021, View Source [SID1234574629]). No consents to any amendment or waiver of the terms of the indenture governing the Old Notes are being solicited in connection with the Exchange Offer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Exchange Offer is being made only to "Eligible Holders," which are holders of Old Notes that certify that they are "qualified institutional buyers", as that term is defined in Rule 144A under the U.S. Securities Act of 1933, as amended (the "Securities Act"), or that are non-U.S. persons, as that term is defined in Rule 902 under the Securities Act (other than "retail investors" in the European Economic Area or the United Kingdom, and investors in any province or territory of Canada that are individuals or that are institutions or other entities that do not qualify as both "accredited investors" and "permitted clients"), as more fully described in the Eligibility Letter. All holders of Old Notes who are not Eligible Holders are "Ineligible Holders".

The table below provides information regarding the Old Notes and the consideration to be paid in the Exchange Offer.

Title of Old
Notes to be
Exchanged Principal
Amount
Outstanding
(mm) CUSIP/ISIN Reference U.S.
Treasury
Security Cash
Payment
Percent
of
Premium(1) Fixed
Spread
(basis
points) Bloomberg
Reference
Screen
5.200% Senior Notes due 2045 $1,750 09062X AD5 / US09062XAD57 1.375% due August 15, 2050 67% 115 FIT1
____________
(1) The Cash Payment Percent of Premium is the portion of the premium that Biogen intends to pay in cash. The premium is equal to the excess of the Total Exchange Consideration for each $1,000 in principal amount of Old Notes over $1,000.

The table below summarizes the terms of the New Notes.

Title of Series
of New Notes Maturity Date Reference U.S.
Treasury Security Fixed Spread
(basis points) Bloomberg
Reference Screen
Senior Notes due 2051 February 15, 2051 1.375% due August 15, 2050 135 FIT1
The Exchange Offer will expire at 5:00 p.m., New York City time, on February 10, 2021, unless extended or earlier terminated by Biogen (the "Expiration Date"). Tenders of Old Notes submitted in the Exchange Offer may be validly withdrawn at any time at or prior to the Expiration Date, unless extended by Biogen, but thereafter will be irrevocable, except in certain limited circumstances where additional withdrawal rights are required by law (as determined by Biogen). The "Settlement Date" will be promptly following the Expiration Date and is expected to be February 16, 2021, unless extended by us.

Concurrently with the Exchange Offer, Biogen also announced today the commencement of a separate cash tender offer (the "Cash Offer"), made only to Ineligible Holders, to purchase Old Notes for cash.

Biogen will deliver New Notes and any cash consideration in exchange for Old Notes accepted for exchange in the Exchange Offer on the Settlement Date.

Upon the terms and subject to the conditions set forth in the Exchange Offer Documents, Eligible Holders who (i) validly tender and do not validly withdraw Old Notes at or prior to the Expiration Date or (ii) deliver a valid notice of guaranteed delivery and all other required documents at or prior to the Expiration Date and tender their Old Notes at or prior to 5:00 p.m., New York City time, on the second business day after the Expiration Date, expected to be on February 12, 2021, pursuant to certain guaranteed delivery procedures and subject in each case to the delivery of the eligibility letter and the tender being in the Authorized Denominations (as defined in the Offering Memorandum), and whose Old Notes are accepted for exchange by Biogen, will receive consideration in the Exchange Offer equal to the Total Exchange Consideration (as defined below).

The Total Exchange Consideration will be calculated at 11:00 a.m., New York City time, on February 10, 2021, unless extended (such date and time, as it may be extended, the "Pricing Time"). The Total Exchange Consideration for the Old Notes, which will be determined in accordance with standard market practice as described in the Offering Memorandum, equates to a yield to the par call date of the Old Notes equal to the Fixed Spread specified for the Old Notes in the table above over the reference yield, which will be based on the bid-side yield of the Reference U.S. Treasury Security specified for the Old Notes in the table above at the Pricing Time.

The Total Exchange Consideration will consist of New Notes and a cash payment equal to the Cash Payment Percent of Premium multiplied by the premium (the excess of the Total Exchange Consideration for each $1,000 in principal amount of Old Notes over $1,000). The issue price of the New Notes, which will be determined in accordance with standard market practice as described in the Offering Memorandum, equates to a yield to maturity equal to the Fixed Spread specified for the New Notes in the table above over the benchmark yield, which will be based on the bid-side yield of the Reference U.S. Treasury Security specified for the New Notes in the table above at the Pricing Time.

Biogen may, at its option, elect to increase or decrease the principal amount of New Notes exchangeable for each $1,000 principal amount of Old Notes tendered and accepted by up to $100 per $1,000 principal amount. Such adjustment would affect the composition, but not the amount, of the Total Exchange Consideration. Biogen expects any such election to be made as of the Pricing Time.

In addition to the Total Exchange Consideration, Biogen also intends to pay in cash accrued and unpaid interest on the Old Notes accepted for exchange from the last interest payment date to, but excluding, the Settlement Date (the "Accrued Coupon Payment"), and amounts due in lieu of fractional amounts of New Notes. Interest will cease to accrue on the Settlement Date for all Old Notes accepted in the Exchange Offer, including those tendered pursuant to the guaranteed delivery procedures. The last interest payment date for the Old Notes is expected to be September 15, 2020.

The complete terms and conditions of the Exchange Offer are set forth in the Exchange Offer Documents, which will be distributed to Eligible Holders in connection with the proposed Exchange Offer. The Exchange Offer is subject to certain conditions, including (i) that, as of the Expiration Date, the combination of the yield of the New Notes and the Total Exchange Consideration for the Old Notes would result in the New Notes and such Old Notes not being treated as "substantially different" under Accounting Standards Codification Subtopic 470-50 (Modifications and Extinguishments), (ii) that, as determined at the Pricing Time, the consummation of the Exchange Offer and the issuance of the New Notes will constitute a "significant modification" of the Old Notes for U.S. federal income tax purposes, (iii) the timely satisfaction or waiver of all of the conditions precedent to the completion of the Cash Offer (the "Cash Offer Completion Condition"), (iv) that the aggregate amount of cash payable by Biogen to Ineligible Holders participating in the Cash Offer is no greater than $50.0 million before giving effect to the Accrued Coupon Payment, (v) that the bid-side yield on the Reference U.S. Treasury Security for the Old Notes in the table above is not more than 2.40% at the Pricing Time, (vi) that the bid-side yield on the Reference U.S. Treasury Security for the Old Notes in the table above is not less than 1.65% at the Pricing Time, (vii) that the aggregate principal amount of New Notes to be issued in the Exchange Offer is at least $300.0 million (the "Minimum Issue Condition"), and (viii) certain customary conditions, as described in the Offering Memorandum.

Biogen will terminate the Exchange Offer if it terminates the Cash Offer, and Biogen will terminate the Cash Offer if it terminates the Exchange Offer. Biogen may not waive the Cash Offer Completion Condition or the Minimum Issue Condition; however, subject to applicable law, Biogen reserves the right, in its reasonable discretion, to waive any of the other conditions.

The Exchange Offer and the issuance of the New Notes have not been registered under the Securities Act, under any other federal, state or other local law pertaining to the registration of securities, or with any securities regulatory authority of any state or other jurisdiction. The New Notes may not be offered or sold except pursuant to an exemption, or in a transaction not subject to, the registration requirements of the Securities Act and any applicable state securities laws.

Only Eligible Holders who have completed and returned the eligibility letter are authorized to receive or review the Offering Memorandum or to participate in the Exchange Offer. For Canadian Eligible Holders, participation in the Exchange Offer is also conditioned upon the completion and return of the Canadian beneficial holder form. There is no separate letter of transmittal for the Exchange Offer.

Eligible Holders are advised to check with any bank, securities broker or other intermediary through which they hold Old Notes as to when such intermediary would need to receive instructions from a beneficial owner in order for that beneficial owner to be able to participate in, or withdraw its instruction to participate in, the Exchange Offer, before the deadlines specified herein and in the Exchange Offer Documents. The deadlines set by any such intermediary, The Depository Trust Company and any applicable clearing system for the submission of tender instructions will be earlier than the relevant deadlines specified herein and in the Exchange Offer Documents.

Global Bondholder Services Corporation is serving as exchange agent and information agent for the Exchange Offer. Documents relating to the Exchange Offer will only be distributed to holders of Old Notes who certify that they are Eligible Holders. Questions or requests for assistance related to the Exchange Offer or for additional copies of the Exchange Offer Documents may be directed to Global Bondholder Services Corporation (866) 470-3900 (U.S. toll-free) or (212) 430-3774 (collect for banks and brokers), or via e-mail at [email protected]. You may also contact your broker, dealer, commercial bank, trust company or other nominee for assistance concerning the Exchange Offer.

The Exchange Offer Documents can be accessed by Eligible Holders who complete and return the eligibility letter at the following link: View Source

This news release is not an offer to sell or buy or a solicitation of an offer to buy or sell any of the securities described herein. The Exchange Offer is being made solely by the Exchange Offer Documents and only to such persons and in such jurisdictions as is permitted under applicable law and the terms and conditions of the Exchange Offer.

On February 4, 2021 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, reported results for the quarter ended December 31, 2020 (Press release, MEI Pharma, FEB 4, 2021, View Source [SID1234574646]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We remain well positioned and focused on advancing zandelisib toward commercialization to deliver an improved therapeutic option to people living with B-cell malignancies," said Daniel P. Gold, Ph.D., president and chief executive officer of MEI Pharma. "We anticipate multiple important milestones from the zandelisib program this year, including topline data from our Phase 2 TIDAL study in the fourth quarter as we closely monitor for potential negative impacts related to the ongoing COVID 19 pandemic on the study, as well as more broadly across our business and development pipeline. In addition we look forward to reporting clinical data updates from the ongoing Phase 1b study and the continued expansion of the zandelisib clinical program evaluating additional indications and combinations, in particular the start of the Phase 3 study evaluating zandelisib in combination with rituximab in patients with second line follicular lymphoma around mid-year."

Dr. Gold continued: "Beyond the zandelisib development program, this year we look forward to the potential for more advances across our pipeline, including clinical data updates from the Phase 1 voruciclib program and our plans to advance ME-344 into a Phase 2 pilot study evaluating patients with solid tumors."

Anticipated Calendar Year 2021 Drug Candidate Pipeline Developments

Zandelisib – PI3K delta inhibitor for the treatment of various B-cell malignancies

Completion of enrollment in the Phase 2 TIDAL study evaluating zandelisib as a monotherapy for patients with relapsed or refractor follicular lymphoma followed by the reporting of top line clinical data from the Phase 2 TIDAL study.
Initiation of a second arm in the Phase 2 TIDAL study enrolling patients with relapsed or refractory marginal zone lymphoma.
Initiation of the Phase 3 study of zandelisib in combination with rituximab evaluating follicular and marginal zone lymphoma patients who received one or more prior lines of treatment; this study is intended to act as the required confirmatory study for the potential accelerated approval of zandelisib in patients with relapsed or refractory follicular lymphoma.
Clinical updates for the Phase 1b study of zandelisib, including the combination with zanubrutinib.
Voruciclib – CDK9 inhibitor for the treatment of B-cell malignancies and acute myeloid leukemia

Program updates, including data from the Phase 1 program evaluating voruciclib.
ME-344 – tumor selective mitochondrial inhibitor

Update plans for a potential Phase 2 pilot study of ME-344 in solid tumors.
Recent and Second Quarter Fiscal Year 2021 Corporate Highlights

In January 2021, the Phase 1b trial arm exploring zandelisib in combination with zanubrutinib (marketed as BRUKINSA), developed by BeiGene, Ltd., enrolled the first patient in a disease specific expansion cohort. The phase 1b study arm evaluating the combination is conducted under a clinical collaboration with BeiGene to evaluate safety and efficacy for the treatment of patients with various relapsed or refractory B-cell malignancies.

In January 2021, MEI announced that the Phase 1b trial arm exploring zandelisib in combination with zanubrutinib in collaboration with BeiGene completed the safety evaluation stage in patients with B-cell malignancies and is expanding into disease specific B-cell malignancy cohorts. The Safety Review Committee recommended moving forward with a dosing regimen found to be generally well tolerated and active following a planned safety analysis.

In October 2020, Kyowa Kirin Co. Ltd. and MEI announced that the first patient was dosed in the pivotal Phase 2 study of zandelisib in patients with indolent B-cell non-Hodgkin’s lymphoma (iNHL) without small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), and Waldenström’s macroglobulinemia (WM) in Japan. This Phase 2, multicenter is intended to support regulatory approval in Japan.
Second Quarter Fiscal Year 2021 Financial Results

As of December 31, 2020, MEI had $180.1 million in cash, cash equivalents, and short-term investments with no outstanding debt.
For the quarter ended December 31, 2020, cash provided by operations was $4.1 million compared to $10.5 million used in operations for the quarter ended December 31, 2019. Cash provided by operations in the 2020 period reflects $20.9 million cash received from the Japanese taxing authorities as a refund of withholding tax associated with the Kyowa Kirin commercialization agreement signed in April 2020.
Research and development expenses were $22.2 million for the quarter ended December 31, 2020, compared to $8.3 million for the quarter ended December 31, 2019. The increase was primarily related to increased development costs associated with zandelisib, including increased activity in the TIDAL study and start-up costs related to the Phase 3 study, as well as increased personnel costs to support clinical trial activities.
General and administrative expenses were $5.7 million for the quarter ended December 31, 2020, compared to $4.2 million for the quarter ended December 31, 2019. The increase primarily relates to general corporate expenses and personnel costs incurred during the quarter ended December 31, 2020.
MEI recognized revenue of $9.2 million for the quarter ended December 31, 2020, compared to $1.0 million for the quarter ended December 31, 2019. The increase in revenue primarily related to the license agreement with Kyowa Kirin and included the recognition of fees allocated to research and development obligations, and reflect Kyowa Kirin’s share of zandelisib costs which were $9.9 million for the quarter ended December 31, 2020.
Net loss was $11.5 million, or $0.10 per share, for the quarter ended December 31, 2020, compared to net loss of $20.2 million, or $0.26 per share for the quarter ended December 31, 2019. The Company had 112,527,860 shares of common stock outstanding as of December 31, 2020, compared with 105,998,677 shares as of December 31, 2019.
The adjusted net loss for the quarter ended December 31, 2020, excluding non-cash expenses related to changes in the fair value of the warrants issued in connection with the May 2018 financing (a non-GAAP measure), was $18.5 million, compared to an adjusted net loss of $11.8 million for the quarter ended December 31, 2019.

On February 4, 2021 PierianDx, the global leader in clinical genomics knowledge, reported a partnership with the Belgian Society of Medical Oncology (BSMO) to study the impact of comprehensive genomic profiling (CGP) on clinical outcomes of late-stage cancer patients (Press release, PierianDx, FEB 4, 2021, View Source [SID1234574667]). As part of the study, nine sites across Belgium will use the PierianDx interpretation and reporting solution, Clinical Genomics Workspace (CGW), to help determine the best therapeutic options for treatment.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Current approaches to precision medicine testing often mean that tests are outsourced to large international organizations or that they are run by independent regional labs, neither of which result in standardized clinical care systems or improved collective knowledge. In response to these challenges, the BSMO has established the BALLETT (Belgian Approach for Local Laboratory Extensive Tumor Testing) study to evaluate the impact of CGP.

CGP uses next-generation sequencing (NGS) to analyze hundreds of genes and biomarkers in tissue samples from biopsies or blood and detect those that are clinically relevant in driving cancer growth. Illumina will provide its CGP panel for tissue samples, TruSight Oncology 500 (TSO500), and NovaSeq 6000 and NextSeq sequencing platforms for the study. Clinical interpretation of the sequencing data will be carried out using the PierianDx Clinical Genomics Workspace (CGW) solution.

CGW provides a streamlined, standardized analysis platform in which EU drug approvals and guidelines are matched to complex genetic variants detected in patient tumor DNA and RNA, all within a GDPR-compliant environment. Using the platform, the nine participating Belgian laboratories can collaboratively review variant pathogenicity and clinical impact for their local samples while also benefiting from the knowledge of other clinical laboratory CGW users from around the world. At the same time, the nine Belgian laboratories will provide this standardized testing and analysis close to the patient’s home, where they receive cancer care, accelerating treatment initiation. As this study will also monitor the patient outcomes during and following treatment, a true indication of those longer-term clinical benefits will be derived.

Dr. Brigitte Maes of the Jessa Hospital in Belgium, Coordinator of BALLETT study said, "As part of Belgium’s broad approach to advancing precision medicine the study will generate valuable insights into the value of CGP versus currently reimbursed sequencing approaches. For example, in addition to genetic mutations that drive cancer formation, CGP will also identify cancers driven by the TMB biomarker which can guide patients towards immunotherapy treatments. This means that the study will give access to additional treatments which may not have been considered through more traditional diagnostic testing."

"Dr. Rakesh Nagarajan, Founder of PierianDx states, "We are ecstatic to be part of this groundbreaking study. The CGW platform is in use by over 25 countries to share knowledge and facilitate better treatments and patient outcomes, and now the clinicians involved in this study will benefit from this collective knowledge while incorporating European-specific data sources, which are curated and maintained by PierianDx." He adds, "Not only will this study measure the impacts of CGP but it will provide a justification, framework, and a blueprint for other clinical laboratories around the world that wish to implement similar initiatives."

On February 4, 2021 Novartis reported that may have jumped out ahead of Merck KGaA with targeted lung cancer med Tabrecta, but the German drugmaker has evened the score (Press release, Merck KGaA, FEB 4, 2021, View Source [SID1234574703]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The FDA Wednesday cleared its drug Tepmetko in non-small cell lung cancer patients with MET exon 14 skipping mutations, whether or not they’ve received prior treatments. The mutation affects about 3% to 4% of NSCLC patients and creates an aggressive form of the disease.

Tepmetko will bear a list price of $20,898.60 for a 30-day supply, which is "within the range of other oral oncolytics for advanced NSCLC," a spokesperson said by email.

U.S. regulators based their decision on data from the phase 2 Vision trial, which showed Tepmetko could spur a benefit in 43% of patients. Previously treated patients continued to respond to the drug for a median 11.1 months, while those new to therapy responded for a median 10.8 months.

RELATED: Merck KGaA beats out Novartis with targeted lung cancer nod for Tepmetko in Japan

The FDA’s nod follows up on a positive decision from the Japanese Ministry of Health, Labour and Welfare, which last March became the first global regulator to green-light a MET inhibitor. Since then, though, the FDA has gotten in on the action with its May 2020 go-ahead for Tabrecta, and now Merck will be taking its product toe-to-toe with Novartis’ in the U.S.

While the Swiss pharma giant has the head start, Merck KGaA has its own advantage to tout: once-daily dosing. Tabrecta tablets are given twice daily at a 400 mg dose, while patients take two 225 mg Tepmetko tablets simultaneously just once per day.

"Our focus now is to ensure Tepmetko is accessible to patients in the United States and fully integrated into clinical practice, given the important advance it represents for indicated patients as an oral once-a-day precision medicine," said Danny Bar-Zohar, M.D., global head of development for Merck KGaA’s healthcare business.

RELATED: Novartis beats Merck KGaA to U.S. finish line with targeted lung cancer drug Tabrecta

To do that, though, first Merck KGaA will have to ramp up MET testing—a goal Novartis shares. Testing for the mutation is usually done as part of next-gen lung cancer sequencing, Ameet Mallik, EVP at Novartis Oncology U.S., said an interview last spring, and at that time, only about 35% of U.S. lung cancer patients were receiving that sequencing upfront.

On February 4, 2021 Codiak BioSciences, Inc. (NASDAQ: CDAK), a clinical-stage biopharmaceutical company focused on pioneering the development of exosome-based therapeutics as a new class of medicines, reported pharmacodynamic (PD) activity results from the healthy volunteer portion of its randomized, placebo-controlled, double-blind Phase 1 trial of the company’s clinical candidate, exoIL-12 (Press release, Codiak Biosciences, FEB 4, 2021, View Source [SID1234574613]). Analyses of skin punch biopsies bordering the subcutaneous injection site of exoIL-12 revealed local retention of immunologically detectable IL-12 at the injection site, and localized pharmacological activity as measured by levels of the T cell attractant chemokine, IP-10, in the skin. IL-12 was not detected in plasma at any dose of exoIL-12 tested and plasma IP-10 was only detectable at the highest, 12 µg dose. Results confirmed the desired localization and retention of IL-12 at the injection site for at least 24 hours, as well as prolonged IP-10 production for 8-15 days depending upon dose.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

exoIL-12 is the first engineered exosome therapeutic candidate to be evaluated in humans and one of two Codiak programs currently in clinical development. exoIL-12 was engineered using the company’s proprietary engEx Platform and designed to display functional IL-12 – a potent anti-tumor cytokine – on the exosome surface using the exosomal protein, PTGFRN, as a scaffold.

"We now have clinical evidence in healthy volunteers of local, IL-12-driven pharmacology without detectable systemic exposure to IL-12 or drug-related adverse events for exoIL-12," said Benny Sorensen, M.D., Ph.D., Senior Vice President and Head of Clinical Development, Codiak. "These results further support the target profile that we are hoping to achieve with this candidate and have enabled us to identify the optimal dose for the next phase of our clinical program in patients with active, early-stage CTCL. Moreover, this data further validates the capacity of our engEx Platform to engineer precise properties into our exosome-based therapeutic candidates that potentially expand their therapeutic index."

These results are consistent with Codiak’s preclinical testing and confirm exoIL-12’s target product profile of local drug retention at the injection site, prolonged local pharmacodynamic activity, and lack of systemic IL-12 exposure. Codiak plans to initiate the next portion of the Phase 1 clinical trial, evaluating the safety and efficacy of exoIL-12, in cutaneous T Cell lymphoma (CTCL) patients at the dose of 6 µg, which Codiak believes to be the optimal pharmacologically active dose based upon this healthy volunteer data and prior preclinical data with exolL-12.

"We are pleased with the data we have obtained with exoIL-12 in healthy human volunteers and look forward to the initiation of trials in CTCL patients," said Douglas E. Williams, Ph.D., President and Chief Executive Officer, Codiak. "It is heartening to see one of the founding principles of Codiak validated in the current trial, namely that engineered exosomes can offer the opportunity to tailor therapeutic payloads to provide an active biological response while at the same time limiting unwanted side effects."

Pharmacodynamic Data from Healthy Volunteers

A total of five cohorts each with five subjects were enrolled, randomized 3:2 active drug to placebo, and dosed in the first part of the Phase 1 study. Each cohort received a subcutaneously administered single ascending dose of exoIL-12: 0.3 µg, 1.0 µg, 3.0 µg, 6.0 µg or 12.0 µg, respectively.

Pharmacodynamic (PD) measurements including skin IL-12 levels post-injection and IL-12 receptor-mediated signaling assessed by induction of IP-10, were measured in skin punch biopsies at a 1.5 cm radius from the subcutaneous injection site. Samples were collected immediately prior to dosing (placebo or exoIL-12) and at 24 hours, Day 8 and Day 15 after administration. Results showed detectable IL-12 near the injection site as much as 24 hours post injection at the 6 µg dose. Samples collected at the 8-day and 15-day time points did not have detectable IL-12. In contrast, doses from 1.0 µg to 12µg (not 0.3 µg) showed significant induction of IP-10 production in the skin detectable for 8-15 days confirming robust and durable local pharmacology. At the highest 12 µg dose, IP-10 was also detectable in the plasma, but not at any of the lower doses. As previously described, no detectable IL-12 was present in plasma and no drug-related adverse events were observed across the entire dose range. These results confirm the prolonged, local activation of the IL-12 signaling cascade and give us confidence that 6 µg is the optimal dose to move forward in the next phase of clinical testing in CTCL patients.

During the planned part two of the Phase 1 trial, repeat doses of exoIL-12 at 6 µg will be administered into the lesions of stage IA-IIB CTCL patients. Patients will be monitored for safety, pharmacokinetic, and PD effects through analysis of blood and tumor biopsies, and for local and systemic anti-tumor efficacy using validated CTCL assessment criteria, including CAILS and mSWAT scores. The study is being conducted in the United Kingdom. Given COVID-19-related restrictions involving new study initiation, Codiak is working closely with study sites to open enrollment and commence dosing of patients when allowable and appropriate. Safety, biomarker and preliminary anti-tumor efficacy results are anticipated by the end of 2021.

In prior clinical trials conducted by others of recombinant IL-12 (rIL-12), CTCL patients have shown single-agent treatment responses (56-74% overall response rate and up to 22% complete responses1). However, the utility of rIL-12 has been greatly limited due to serious adverse events caused by systemic exposure. To overcome these limitations, exoIL-12 was designed to facilitate dose control of IL-12 and limit systemic exposure and associated toxicity by localizing IL-12 in the tumor microenvironment (TME) in order to potentially expand the therapeutic index.

There is currently no standard of care treatment for early-stage CTCL. Physicians often employ a variety of non-specific interventions, including repetitive radiation therapy, photo therapy, high-potency steroids and local chemotherapy to inhibit tumor growth and halt disease progression. There is a need for treatments that can induce local as well as systemic anti-tumor activity.

About exoIL-12

exoIL-12 is Codiak’s exosome therapeutic candidate engineered to display fully active IL-12 on the surface of the exosome, using the exosomal protein, PTGFRN, as a scaffold, and designed to facilitate potent local pharmacology at the injection site with precisely quantified doses. By limiting systemic exposure of IL-12 and associated toxicity, Codiak hopes to enhance the therapeutic index with exoIL-12, delivering a more robust tumor response, dose control and an improved safety profile.

Codiak intends to focus development of exoIL-12 on tumors that have, in previous clinical testing, shown clinical responses to rIL-12 used as a monotherapy. This list includes CTCL, melanoma, Merkel cell carcinoma, Kaposi sarcoma, glioblastoma multiforme, triple negative breast cancer, among others.