SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of report (Date of earliest event reported): January 4, 2021
Pandion Therapeutics, Inc.
(Exact Name of Registrant as Specified in Charter)
(State or Other Jurisdiction
134 Coolidge Avenue
|(Address of Principal Executive Offices)||(Zip Code)|
Registrants telephone number, including area code: (617) 393-5925
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Securities registered pursuant to Section 12(b) of the Act:
|Common Stock, par value $0.001 per share||PAND||Nasdaq Global Select Market|
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
|Item 7.01|| |
Regulation FD Disclosure.
On January 4, 2021, Pandion Therapeutics, Inc. (the Company) issued a press release announcing topline data from its Phase 1a clinical trial of PT01 in healthy volunteers. A copy of the press release is attached hereto as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.
The Company will host a conference call to discuss the topline data on January 4, 2021 at 8:30 a.m. ET, and a webcast of the call will be available through the investor relations section of the Companys website.
On January 4, 2021, the Company posted a presentation on the Investors & Media section of the Companys website (www.pandiontx.com). The information contained in, or that can be accessed through, the Companys website is not a part of this filing. A copy of the presentation is attached as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.
The information in this Item 7.01, including Exhibits 99.1 and 99.2 attached hereto, shall not be deemed filed for purposes of Section 18 of the Securities Exchange Act of 1934 (the Exchange Act) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933 or the Exchange Act, except as expressly set forth by specific reference in such a filing.
|Item 9.01|| |
Financial Statements and Exhibits.
The following exhibit is furnished herewith:
|99.1||Press Release issued by the Company on January 4, 2021|
|99.2||Presentation dated January 4, 2021|
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
|PANDION THERAPEUTICS, INC.|
|Date: January 4, 2021||By:|
Chief Executive Officer
Pandion Therapeutics Announces Positive Top-Line Phase 1a Clinical Data Showing PT101 was Well-Tolerated and Selectively Expanded Regulatory T cells
-Phase 1a trial achieved primary objective of safety and tolerability
-PT101 induced potent and selective expansion of regulatory T cells exceeding levels associated with clinical benefit in third-party clinical trials across multiple autoimmune diseases
-PT101 maintained selectivity for regulatory T cells at all doses tested
-Phase 1a/2b clinical trial in ulcerative colitis expected to start mid-2021 and Phase 2 clinical trial in systemic lupus erythematosus expected to start second half 2021
-Phase 1a results to be presented in a conference call scheduled today at 8:30 a.m. ET
WATERTOWN, Mass. January 4, 2021 Pandion Therapeutics (Nasdaq: PAND) today announced positive top-line data from its Phase 1a single-dose, healthy volunteer clinical trial, demonstrating proof of mechanism of PT101, an engineered IL-2 mutein fused to a protein backbone, in development for ulcerative colitis (UC), systemic lupus erythematosus (SLE), and other autoimmune diseases.
In the Phase 1a clinical trial, PT101 was observed to be well-tolerated and there were no serious adverse events.
PT101 selectively expanded total regulatory T cells (Tregs), with a mean maximal increase up to of 3.6-fold over baseline. A subset of activated Tregs with high CD25 expression, known as CD25 bright Tregs, expanded, with a mean maximal increase of up to 72.5-fold over baseline. There was no evidence of expansion of natural killer T (NK) cells and pro-inflammatory conventional T (Tconv) at any dose studied. In third-party clinical trials using low-dose native IL-2, a two-fold increase in total Tregs was associated with clinical benefit across multiple autoimmune diseases.
Native IL-2 has been the subject of several clinical trials across a range of autoimmune diseases due to its ability to activate a normal immune regulatory response and improve disease activity. However, its therapeutic use has been hampered by native IL-2s undesired activation of the pro-inflammatory side of the immune system, said Scott Snapper, M.D., Ph.D., Chief, Division of Gastroenterology, Hepatology and Nutrition; Director, Inflammatory Bowel Disease Center at Boston Childrens Hospital and Professor of Medicine at Harvard Medical School. PT101s high selectivity for and expansion of Tregs could allow for a fulsome exploration of the potential of this mechanism in autoimmune diseases, and I look forward to seeing its continued clinical development by Pandion.
The Phase 1a randomized, blinded clinical trial enrolled 56 healthy volunteers across seven cohorts who each received a single subcutaneous fixed dose of PT101 ranging from 1 mg to 10 mg, or placebo. Subjects were followed for 28 days after dosing and evaluated for safety and tolerability as well as pharmacokinetic and pharmacodynamic measures. These measures were selected to assess the potency and selectivity of PT101 in order to establish proof of mechanism.
All adverse events observed in the trial were low grade (Grade 1 or 2) and self-limited. The most common adverse events were skin reactions of itching, redness or pain near or around the site of injection of PT101. In laboratory tests, some subjects showed transient elevations of eosinophils, a type of white blood cell, that were self-limited in nature and did not require medical treatment. The Company believes the eosinophil elevation may be related to the IL-2 mechanism of PT101.
Expansion of both total Tregs and the CD25 bright Treg subset was observed throughout the dose range, as depicted in the table below. Peak expansion of Tregs was observed between days 8 and 10. At doses of 3.5 mg and above, PT101 induced a two-fold or greater expansion of total Tregs in more than 80% of subjects. Tregs returned to baseline or near-baseline over the 28-day follow-up period, supporting the Companys plan to utilize a dosing regimen of every four weeks in future clinical trials.
Mean peak fold expansion of Total Tregs (SEM)
|1.4 (±0.08)||1.8 (±0.31)||3.6 (±0.66)||3.5 (±0.37)||3.4 (±0.57)||3.2 (±0.24)|
Mean peak fold expansion of CD25 bright Treg subset (SEM)
|3.4 (±0.49)||8.6 (±3.33)||72.5 (±26.39)||54.1 (±8.89)||51.6 (±17.17)||37.4 (±6.93)|
SEM= standard error of the mean
These data show PT101 meaningfully expanded regulatory T cells while maintaining a high degree of selectivity, commented John Sundy, M.D., Ph.D., Chief Medical Officer of Pandion Therapeutics. We believe this combined potency and selectivity could provide meaningful clinical benefit for patients with many different autoimmune diseases. Therefore, following the completion of the regulatory process, we plan to initiate a Phase 1b/2a clinical trial in patients with UC in mid-2021 and a Phase 2 clinical trial in patients with SLE in the second half of 2021.
Full data from the trial are expected to be presented at upcoming medical meetings.
Conference Call and Webcast Information
Pandion will hold a conference call and webcast to review the Phase 1a clinical data of PT101 today at 8:30 a.m. ET. To participate in the conference call, please dial +1 833-693-0533 (US toll-free number) or +1 661-407-1572 (international participants) and use the passcode 6051816. Investors may also access a live audio webcast of the call and slides for the discussion via the Investors & News section of the Companys website, www.pandiontx.com. A replay of the webcast will be available on the Companys website shortly after the presentation ends.
About Regulatory T Cells (Tregs)
Tregs act as a control node within the immune system and can inhibit the activity of several different pro-inflammatory immune cell types. Tregs are critical for self-tolerance, or the ability of the immune system to recognize a hosts cells and not produce an immune attack against them. Defects in Tregs result in multi-organ inflammation and their dysfunction is associated with many autoimmune diseases. Multiple third-party clinical trials suggest that expansion of Tregs by low-dose IL-2 can benefit patients with autoimmune diseases.
CD25 bright Tregs are a subset of Tregs with high expression of CD25 (also known as the IL-2 receptor alpha subunit). It has been reported that CD25 bright Tregs may be a more active subset of Tregs with enhanced immune regulatory function.
PT101 is an engineered IL-2 mutein fused to a protein backbone designed to selectively activate and expand regulatory T cells for the treatment of autoimmune diseases. In autoimmune diseases, the immune system inappropriately attacks a hosts cells, and targeting regulatory T cells could allow the immune system to regain control and return to homeostasis. PT101 has completed a Phase 1a clinical trial, which met its primary endpoint of safety and tolerability. In the trial, PT101 demonstrated proof of mechanism by selectively expanding Tregs in healthy volunteers.
About Pandion Therapeutics
Pandion Therapeutics is developing novel therapeutics designed to address the unmet needs of patients living with autoimmune diseases. Pandions TALON (Therapeutic Autoimmune reguLatOry proteiN) drug design and discovery platform enables the company to create a pipeline of product candidates using immunomodulatory effector modules, with the ability to also combine an effector module with a tissue-targeted tether module in a bifunctional format. Pandions lead product candidate PT101, a combination of an interleukin-2 mutein effector module with a protein backbone, is designed to selectively expand regulatory T cells systemically, without activating proinflammatory cells, such as conventional T cells and natural killer cells. Pandion is continuing to develop and expand its library of effector and tether modules as part of its earlier-stage research and discovery pipeline. For more information, please visit www.pandiontx.com and engage with us on Twitter @PandionTX or on LinkedIn.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release, including statements regarding PT101 as a potential treatment for patients with autoimmune diseases, the timing of future clinical trials of PT101, the Companys strategy and clinical development plans, timelines and prospects, are forward-looking statements. The words anticipate, believe, continue, could, estimate, expect, intend, may, plan, potential, predict, project, should, target, will, would and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on managements current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with Pandions ability to obtain and maintain necessary approvals from the FDA and other regulatory authorities; initiate preclinical studies and clinical trials of PT101 and its other product candidates; advance PT101 and its other product candidates in preclinical research and clinical trials; replicate in clinical trials positive results found in preclinical studies; advance the development of its product candidates under the timelines it anticipates in current and future clinical trials; obtain, maintain or protect intellectual property rights related to its product candidates; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the
forward-looking statements, see the Risk Factors section, as well as discussions of potential risks, uncertainties and other important factors, in the Companys most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Companys views as of the date hereof and should not be relied upon as representing the Companys views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will cause the Companys views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so.
The Yates Network
Nasdaq: pand January 2021 Exhibit 99.2
This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the development status of the Company’s product candidates and the timing of availability of clinical trial data. All statements, other than statements of historical facts, contained in this presentation, including statements regarding the Company’s strategy, future operations, future financial position, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with Pandion’s ability to obtain and maintain necessary approvals from the FDA and other regulatory authorities; initiate preclinical studies and clinical trials of its product candidates; advance its product candidates in preclinical research and clinical trials; replicate in clinical trials positive results found in preclinical studies; advance the development of its product candidates under the timelines it anticipates in current and future clinical trials; obtain, maintain or protect intellectual property rights related to its product candidates; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the “Risk Factors” section, as well as discussions of potential risks, uncertainties and other important factors, in the Company’s most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this presentation represent the Company’s views as of the date hereof and should not be relied upon as representing the Company’s views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such data and estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. Neither Pandion nor its affiliates, advisors or representatives makes any representation as to the accuracy or completeness of that data or undertakes to update such data after the date of this presentation. Forward-Looking Statements and Disclaimers
Phase 1a single dose, randomized, blinded clinical trial in 56 healthy volunteers PT101 was well-tolerated; no serious adverse events observed PT101 selectively expanded total regulatory T cells (Treg) to levels exceeding those associated with clinical benefit in third-party clinical trials of low-dose IL-2 At doses 3.5 mg and above, >80% of subjects achieved 2-fold or greater Treg expansion Mean maximum total Tregs expanded up to 3.6-fold above baseline Mean maximum CD25bright subset of Tregs expanded up to 72.5-fold above baseline Treg expansion profile supports every four-week dosing PT101 was selective for Tregs; no evidence of expansion of natural killer (NK) cells or pro-inflammatory conventional T cells (Tconv) at any dose level Top-Line Data from Phase 1a Clinical Trial of PT101
Regulate multiple immune cells Involved in tissue repair and regeneration Critical for self-tolerance Defects cause multi-organ inflammation Dysfunction associated with IBD, SLE, MS, T1D, other diseases Multiple third-party clinical trials suggest Treg expansion with IL-2 can benefit multiple autoimmune diseases Tregs Play a Key Role in Immune Homeostasis Tregs Regulate Activated Immune Cells Treg Tconv APCs NK Cells B Cells
Low Dose IL-2 as a Strategy for Activating Tregs IL-2 critical growth factor for all T cells Tregs have high sensitivity for IL-2 due to constitutive expression of IL-2Rαβγ trimer Low-dose IL-2 treatment has shown clinical benefit in multiple autoimmune diseases High Dose IL-2 Pro-inflammatory for oncology High IL-2 concentrations activate Tconv and NK cells Anti-inflammatory for autoimmunity Low IL-2 concentrations selectively activate Tregs Treg IL-2Rαβγ Trimer IL-2Rβγ Dimer Tconv or NK Cells Wild-type IL-2 Concentration Cellular Activation (%) Low Dose IL-2
Academic Data on Low Dose IL-2* Support PT101 Mechanism Dose A Dose B Dose C # of Patients 4 15 5 Aldesleukin Dose 106 IU/m2/d** 0.3 1.0 1.5 ≥2x Treg Expansion*** % of pts 50% 100% 100% and Tconv activation Clinical Response Rate week 8 25% 60% 0% Clinical Remission Rate week 8 25% 27% 0% *Aldesleukin **millions of international units per meter squared per day ***achieved at least once during treatment vs baseline Source: adapted from third party, Allegretti, et al, DDW May 5, 2020, Abstract #1026 Supports PT101 mechanism Low dose IL-2 showed clinical benefit across multiple autoimmune indications Snapper data show need for Treg selectivity Narrow window before loss of Treg selectivity and Tconv activation Academic data support low-dose IL-2 in many autoimmune diseases Improvements seen in disease scores for UC, systemic lupus erythematosus, psoriasis, and ankylosing spondylitis Low Dose IL-2 Expanded Tregs & Showed Promise in UC Independent published data from Scott Snapper
Optimization and Selection of PT101 Selectivity Enhance with structure-based engineering Fc Fusion Best TALON format for Treg selectivity 1Reduce IL-2Rβ Affinity 2Increase IL-2Rα Affinity 3Optimize Format IL-2Rb IL-2Ra IL-2Rg N88D PT101 IL-2 Mutein N88D Start with best known mutation for Treg selectivity
Activated immune cells PT101 is selective for Tregs IL-2Rβγ PT101 Treg IL-2Rβγ IL-2Rα Tconv PT101 activates and expands Tregs NK Cells PT101 Selectively Activates Tregs vs Tconv and NK Cells PT101 Concentration Cellular Activation (%) PT101 selectively activates Tregs due to constitutive expression of IL-2Rαβγ trimer Immune cells with only IL-2Rβγ dimer are not activated Activated immune cells are attenuated
PT101 Phase 1a Trial Design *PK = pharmacokinetics; PD = pharmacodynamics Design Phase 1a Single Ascending Dose Study Blinded; randomized design Single site; dedicated Phase 1 unit 56 healthy volunteers across 7 cohorts 8 subjects per cohort (6 PT101 : 2 placebo) Endpoints Safety, Tolerability, and Mechanism Safety and tolerability Pharmacokinetics Treg / Tconv / NK at multiple time points Screening Baseline Follow-up Period Treg / Tconv / NK at multiple time points D-10 D1 D28 Dose Placebo 1 mg 3.5 mg 5 mg 7.5 mg 10 mg # Subjects 14 6 12 12 6 6
No serious AEs, deaths, dose-limiting toxicity, or early study discontinuation No clinically important changes in vital signs or ECGs All AEs were Grade 1 or 2, mild to moderate, and self-limited Some subjects had a transient elevation in eosinophils that were self-limited, not considered adverse, and believed may be related to PT101’s mechanism Dose proportional exposure; half-life ~20-28 hours No induction of anti-drug antibodies was observed PT101 was Well Tolerated; No Serious AEs Observed Placebo (n=14) 1 mg (n=6) 3.5 mg (n=12) 5 mg (n=12) 7.5 mg (n=6) 10 mg (n=6) Number with any AE (%) 3 (21%) 2 (33%) 4 (33%) 4 (33%) 4 (67%) 4 (67%) Most common AEs were related to injection site reactions Self-limited skin reactions extending beyond injection site occurred in some subjects at doses of ≥7.5 mg Mild Grade 1 dyspnea was reported in three subjects, with no physical exam findings, no limitation in activity, and no requirement for treatment Grade 2 AEs were only observed in the 10 mg group AE= adverse event
PT101 Expanded Total Tregs in Healthy Volunteers Mean Maximum Expansion Placebo 1 mg 3.5 mg 5 mg 7.5 mg 10 mg Fold Change PT101 expanded total Tregs with up to a mean maximum fold change of 3.6 ≥2-fold total Treg expansion associated with clinical benefit in third-party clinical trials in multiple autoimmune diseases Total Tregs Time (days) Fold Change Single dose Values are mean (SEM) fold change in absolute cell count over baseline Baseline: mean of measurement on Days -10 and 1 pre-dose for each subject Common datapoints for cohorts 1-7 are shown; data was also collected from cohorts 4-7 on Days 6, 10, 12, and 22 (not shown) Mean maximum value calculated using all timepoints Placebo 1 mg 3.5 mg 5 mg 7.5 mg 10 mg
PT101 Markedly Expanded the CD25bright Treg Subset Mean Maximum Expansion PT101 expanded the CD25bright Treg subset with up to a mean maximum fold change of 72.5 It has been reported that CD25bright Tregs may be a more active subset of Tregs with enhanced immune regulatory function Placebo 1 mg 3.5 mg 5 mg 7.5 mg 10 mg Fold Change CD25bright Treg Subset Time (days) Fold Change Values are mean (SEM) fold change in absolute cell count over baseline Baseline: mean of measurement on Days -10 and 1 pre-dose for each subject Common datapoints for cohorts 1-7 are shown; data was also collected from cohorts 4-7 on Days 6, 10, 12, and 22 (not shown) Mean maximum value calculated using all timepoints Single dose Placebo 1 mg 3.5 mg 5 mg 7.5 mg 10 mg
Robust Treg Response Rate Observed with PT101 Fold Change Placebo (n=14) 1 mg (n=6) 3.5 mg (n=12) 5 mg (n=12) 7.5 mg (n=6) 10 mg (n=6) 2x or greater 7% 33% 83% 83% 100% 100% 3x or greater 0% 0% 58% 75% 33% 50% 4x or greater 0% 0% 24% 42% 33% 17% More than 80% of subjects achieved 2-fold or greater total Treg expansion at doses ≥3.5 mg A significant proportion of subjects achieved 3 to 4-fold Treg expansion at doses of ≥3.5 mg Total Treg Expansion Responder Analysis (% of Subjects per Dose)
PT101 Maintained Treg Selectivity Throughout Dose Range Values are mean (SEM) 50%tile and 95%tile are derived from analysis of 129 subjects’ Day -10 screening samples in Cohorts 1-7 Common datapoints for cohorts 1-7 are shown; data was also collected from cohorts 4-7 on Days 6, 10, 12, and 22 (not shown) CD8 T Cells Time (days) Absolute Number (cells/ul) 95%tile 50%tile NK Cells Time (days) Absolute Number (cells/ul) 95%tile 50%tile CD4 Tconv Cells Time (days) Absolute Number (cells/ul) 95%tile 50%tile Single dose NK cells, CD4 Tconv cells, and CD8 T cells remained within normal range at all doses tested Placebo 1 mg 3.5 mg 5 mg 7.5 mg 10 mg
PT101 was well-tolerated; no serious adverse events observed PT101 selectively expanded total Tregs to levels exceeding those associated with clinical benefit in third-party clinical trials of low-dose IL-2 At doses 3.5 mg and above, >80% of subjects achieved 2-fold or greater Treg expansion Mean maximum total Tregs expanded up to 3.6-fold above baseline Mean maximum CD25bright subset of Tregs expanded up to 72.5-fold over baseline Treg expansion profile supports every four-week dosing PT101 was selective for Tregs; no evidence of expansion of NK cells or pro-inflammatory conventional T cells at any dose level Expect to initiate Phase 1b/2a clinical trial in patients with ulcerative colitis in mid-2021 and a Phase 2 clinical trial in patients with systemic lupus erythematosus in 2H 2021 Conclusion