8-K
Passage BIO, Inc. (PASG)
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): August 5, 2021
PASSAGE BIO, INC.
(Exact name of registrant as specified in its charter)
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| Delaware | 001-39231 | 82-2729751 |
| (State or other jurisdiction<br><br>of incorporation) | (Commission<br><br>File Number) | (IRS Employer<br><br>Identification No.) |
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|---|---|
| One Commerce Square<br>2005 Market Street, 39^th^Floor<br>Philadelphia, PA | 19103 |
| (Address of principal executive offices) | (Zip Code) |
(267) 866-0311
(Registrant’s telephone number, including area code)
N/A
(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:
| ☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
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| ☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
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| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
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| ☐ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
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Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading symbol(s) | Name of each exchange on which registered |
|---|---|---|
| Common Stock, $0.0001 Par Value Per Share | PASG | The Nasdaq Stock Market LLC<br>(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 2.02 Results of Operations and Financial Condition.
On August 5, 2021, Passage Bio, Inc. issued a press release announcing its financial results for the quarter ended June 30, 2021. A copy of the press release is attached as Exhibit 99.1 to this report.
The information in this Item 2.02, including Exhibit 99.1 to this report, shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended (the “Securities Act”). The information contained in this Item 2.02 and in the accompanying Exhibit 99.1 shall not be incorporated by reference into any other filing under the Exchange Act or under the Securities Act, except as shall be expressly set forth by specific reference in such filing.
Item 7.01 Regulation FD Disclosure.
On August 5, 2021, the Company also updated its corporate presentation. A copy of the corporate presentation is attached as Exhibit 99.2 to this report.
The information in this Item 7.01, including Exhibit 99.2 to this report, shall not be deemed to be “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act. The information contained in this Item 7.01 and in the accompanying Exhibit 99.2 shall not be incorporated by reference into any other filing under the Exchange Act or under the Securities Act, except as shall be expressly set forth by specific reference in such filing.
Item 9.01 Financial Statements and Exhibits.
(d)Exhibits
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| Exhibit<br>Number | Description | |
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| 99.1 | | Press release issued by Passage Bio, Inc. regarding its financial results for the quarter ended June 30, 2021, dated August 5, 2021. |
| 99.2 | | Corporate Presentation. |
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SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| | PASSAGE BIO, INC. | ||
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| Date: August 5, 2021 | By: | /s/ Bruce Goldsmith, Ph.D. | |
| | | Chief Executive Officer, President and Principal Financial Officer |
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Exhibit 99.1
Passage Bio Reports Second Quarter 2021 FinancialResults and Provides Recent Business Highlights
| - | Expanded strategic collaboration with University of Pennsylvania’s Gene Therapy Program to advance genetic medicines for large CNS diseases, initially focused on Alzheimer’s Disease and Temporal Lobe Epilepsy |
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| - | Expect to deliver three key clinical milestones in second half of 2021: |
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| o | Dose first patients in global Phase 1/2 trials for PBFT02 and PBKR03 in 3Q21 |
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| o | Report initial safety and 30-day biomarker data from Imagine-1 global Phase 1/2 trial of PBGM01 for the treatment of infantile GM1 in 4Q21 |
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| - | Opened new CMC research and development site in Hopewell, N.J. |
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| - | Appointed three new executives – chief commercial officer, chief financial officer and chief medical officer |
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| - | Management to host conference call today at 8:30 a.m. ET |
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Philadelphia, PA – August 5, 2021 – Passage Bio, Inc. (Nasdaq: PASG), a clinical-stage genetic medicines company focused on developing transformative therapies for central nervous system (CNS) disorders today reported financial results for the second quarter ended June 30, 2021 and provided recent business highlights.
“As we advance our pipeline and invest in our capabilities, we are committed to becoming a leader in developing transformative genetic medicines for people with CNS disorders,” said Bruce Goldsmith, Ph.D., president and chief executive officer of Passage Bio. “I am extremely excited about the opportunity that the expanded partnership with Penn’s Gene Therapy Program creates for us to address the significant unmet needs of not only rare but also larger patient populations impacted by devastating CNS disorders. Our expanded research collaboration will include the identification of relevant biological targets for genetic modulation. We also have continued to build the talent of our company so that we can efficiently and effectively execute our clinical programs and new research opportunities. I’m also very pleased with our recent executive appointments.”
James M. Wilson, M.D., Ph.D., chief scientific advisor for Passage Bio; Rose H. Weiss professor and director, Orphan Disease Center; professor in Departments of Medicine and Pediatrics, Perelman School of Medicine; and director of University of Pennsylvania’s Gene Therapy Program (GTP), said: “We are delighted with the progress that has been made through our collaborative R&D relationship with Passage Bio. Extending the scope of our collaboration is a logical next step and will allow us to deploy our gene therapy technologies into potential treatments for even larger patient populations that suffer from severe disabling and lethal neurological diseases.”
Eliseo Salinas, M.D., MSc., chief R&D officer of Passage Bio, added: “As we broaden our CNS pipeline, we also continue to prioritize execution against our three lead clinical development programs. We are making steady progress opening our global network of clinical sites across nine countries and three continents and managing through lingering COVID-19 pandemic impacts. We continue to expect to dose the first patients in the third quarter for our clinical trials for frontotemporal dementia with granulin mutations, upliFT-D; and Krabbe disease, GALax-C. We also expect to report initial safety and 30-day biomarker data in the fourth quarter for our ongoing Imagine-1 global trial for GM1 gangliosidosis.
We’re excited by the momentum we’re building in our journey to deliver life-transforming therapies for patients with rare CNS disorders.”
Recent Highlights
| ● | Passage Bio and Penn’s GTP expanded strategic collaboration and license agreement to advance genetic medicines for large patient populations: The agreement establishes new research programs to discover and develop new genetic medicines for Alzheimer’s Disease and Temporal Lobe Epilepsy as well as additional large CNS indications upon mutual agreement. These new programs include a collaborative initial discovery phase focused on identifying relevant biological targets for these two diseases. The collaboration term has also been extended by an additional year to 2026. As part of the expansion, Penn will receive a $5.0 million upfront payment as well as additional royalties and milestone payments for products that may arise from the newly added research programs. |
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| ● | Global Phase 1/2 clinical trials for both PBFT02 and PBKR03 on track to dose first patients in third quarter of 2021: The company expects to report initial safety and 30-day biomarker data in the first half of 2022 for the global clinical trials upliFT-D for PBFT02 for frontotemporal dementia with granulin mutations (FTD-GRN), and GALax-C for PBKR03 for Krabbe disease. Genetic testing to help identify FTD patients is being offered through InformedDNA, a leading genetics services organization; and through Invitae, a leading medical genetics company, for patients suspected of having Krabbe disease. |
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| ● | Imagine-1 global Phase 1/2 clinical trial of PBGM01 for the treatment of infantile GM1 gangliosidosis progressing toward initial safety and 30-day biomarker data readout in 4Q21: In April 2021, the company announced that the first patient was dosed for the treatment of infantile GM1 gangliosidosis (GM1) in the global Imagine-1 trial. During the second quarter of 2021, the company advanced clinical site activation efforts and plans to open additional sites in the third quarter. |
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| ● | PBFT02 received European Commission Orphan Designation for the treatment of FTD-GRN: This designation provides Passage Bio with certain potential benefits, including clinical protocol assistance, reduced regulatory fees, research grants and up to 10 years of market exclusivity following regulatory approval. |
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| ● | New gene therapy R&D lab opened in Hopewell, N.J.: The Chemistry, Manufacturing and Controls (CMC) laboratory, called Princeton West, will support analytical development, clinical product testing and assay validation for Passage Bio’s novel gene therapy candidates. |
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| ● | New executive leadership appointments announced: |
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| o | Maria Törnsén joined Passage Bio as chief commercial officer, effective July 19. Ms. Törnsén, who has nearly 20 years of global commercial experience, was most recently at Sarepta Therapeutics, where she was senior vice president, general manager, U.S. |
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| o | Simona King will join Passage Bio as chief financial officer (CFO), effective August 23. Ms. King, former executive vice president and CFO at Tmunity Therapeutics, has more than 20 years of pharmaceutical and biotech strategic finance experience. |
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| o | Mark Forman, M.D., Ph.D., joined Passage Bio as chief medical officer, effective July 30, from the Alzheimer’s Drug Discovery Foundation, where he oversaw the drug discovery and development portfolio. Dr. Forman has nearly 20 years of experience in translational research for neurological disorders in both corporate and academic settings, having worked at Acadia, Merck and the University of Pennsylvania. |
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| ● | Derrell D. Porter M.D., elected to Passage Bio board of directors in May 2021. Dr. Porter, who brings strong corporate strategy, product development and commercial experience, serves on the Audit Committee of the board. He is founder and chief executive officer of Cellevolve Bio, a cell therapy company focused on transforming investigational CNS, oncology and transplant therapies into commercial products. |
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Anticipated Upcoming Milestones
| ● | Dose first patient in Phase 1/2 FTD-GRN trial in 3Q21; report initial safety and 30-day biomarker data in 1H22. |
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| ● | Dose first patient in Phase 1/2 Krabbe trial in 3Q21; report initial safety and 30-day biomarker data in 1H22. |
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| ● | Report initial safety and 30-day biomarker data from Phase 1/2 PBGM01 trial in 4Q21. |
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| ● | Continue to advance early-stage programs for PBML04 (Metachromatic leukodystrophy), PBLA05 (Amyotrophic lateral sclerosis) and PBCM06 (Charcot-Marie-Tooth Disease Type 2A), and an undisclosed adult CNS program. |
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Second Quarter 2021 Financial Results
| ● | **Cash Position:**Cash, cash equivalents and marketable securities were $407.8 million as of June 30, 2021, as compared to $304.8 million as of December 31, 2020. The company expects current cash and cash equivalents to fund operations for at least the next 24 months. |
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| ● | **Research and Development (R&D) Expenses:**R&D expenses were $33.1 million for the second quarter ended June 30, 2021, compared to $19.9 million for the same quarter in 2020. |
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| ● | General and Administrative (G&A) Expenses: G&A expenses were $15.4 million for the second quarter ended June 30, 2021, compared to $7.4 million for the same quarter in 2020. |
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| ● | Net Loss: Net loss was $48.4 million, or a net loss of $0.90 per basic and diluted share, for the second quarter ended June 30, 2021, compared to $27.2 million, or a net loss of $0.60 per basic and diluted share, for the same quarter in 2020. |
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Conference Call Details
Passage Bio will host a conference call and webcast today at 8:30 a.m. ET. To access the live conference call, please dial 833-528-0605 (domestic) or 830-221-9711 (international) and reference conference ID number 4037236. A live audio webcast of the event will be available on the Investors & News section of Passage Bio’s website at investors.passagebio.com. The archived webcast will be available on Passage Bio's website approximately two hours after the completion of the event and for 30 days following the call.
About Passage Bio
At Passage Bio (Nasdaq: PASG), we are on a mission to provide life-transforming genetic medicines for patients with CNS diseases that replace their suffering with boundless possibility, all while building lasting relationships with the communities we serve. Based in Philadelphia, PA, our company has established a strategic collaboration and licensing agreement with the renowned University of Pennsylvania’s Gene Therapy Program to conduct our discovery and IND-enabling preclinical work. This provides our team with enhanced access to a broad portfolio of gene therapy candidates and future gene therapy innovations that we then pair with our deep clinical, regulatory, manufacturing and commercial expertise to rapidly advance our robust pipeline of optimized gene therapies into clinical testing. As we work with speed and tenacity, we are always mindful of patients who may be able to benefit from our therapies. More information is available at www.passagebio.com.
Penn Financial Disclosure
Dr. Wilson is a chief scientific advisor, collaborator, consultant and co-founder of Passage Bio. As such, he holds an equity stake in the company, his laboratory at Penn receives sponsored research funding from Passage Bio, and as an inventor of certain Penn intellectual property that is licensed to Passage Bio, Dr. Wilson may receive additional financial benefits in the future. The University of Pennsylvania receives sponsored research funding from Passage Bio and has licensed intellectual property to the company that may result in future financial returns to Penn**.**
Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations regarding our new research program with Penn’s Gene Therapy Program in large indications, including whether the expanded collaboration will result in any new product candidates in the selected targets or other indications; our expectations about timing and execution of anticipated milestones, including initiation of clinical trials and the availability of clinical data from such trials; our expectations about our collaborators’ and partners’ ability to execute key initiatives; our expectations about manufacturing plans and strategies; our expectations about cash runway; and the ability of our lead product candidates to treat their respective target CNS disorders. These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “might,” “plan,” “potential,” “possible,” “will,” “would,” and other words and terms of similar meaning. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop and obtain regulatory approval for our product candidates; the timing and results of preclinical studies and clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early
stage clinical trials may not be predictive of results in later stage clinical trials; failure to protect and enforce our intellectual property, and other proprietary rights; our dependence on collaborators and other third parties for the development and manufacture of product candidates and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; and the other risks and uncertainties that are described in the Risk Factors section in documents the company files from time to time with the Securities and Exchange Commission (SEC), and other reports as filed with the SEC. Passage Bio undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.
For further information, please contact:
Investors:
Stuart Henderson
Passage Bio
267.866.0114
shenderson@passagebio.com
Media:
Gwen Fisher
Passage Bio
215.407.1548
gfisher@passagebio.com
Passage Bio, Inc.
Balance Sheets
(Unaudited)
| (in thousands, except share data) | **** | June 30, 2021 | **** | December 31, 2020 | **** | ||
|---|---|---|---|---|---|---|---|
| Assets | | | | | | | |
| Current assets: | | | | | | | |
| Cash and cash equivalents | | $ | 215,457 | | $ | 135,002 | |
| Marketable securities | | | 192,343 | | | 169,815 | |
| Prepaid expenses and other current assets | | | 3,863 | | | 1,405 | |
| Prepaid research and development | | | 7,176 | | | 10,961 | |
| Total current assets | | | 418,839 | | | 317,183 | |
| Property and equipment, net | | | 13,480 | | | 2,795 | |
| Other assets | | | 7,206 | | | 8,029 | |
| Total assets | | $ | 439,525 | | $ | 328,007 | |
| Liabilities and stockholders’ equity | | | | | | | |
| Current liabilities: | | | | | | | |
| Accounts payable | | $ | 16,402 | | $ | 5,265 | |
| Accrued expenses and other current liabilities | | | 14,847 | | | 15,910 | |
| Total current liabilities | | | 31,249 | | | 21,175 | |
| Deferred rent | | | 6,007 | | | 2,077 | |
| Other liabilities | | | — | | | 41 | |
| Total liabilities | | | 37,256 | | | 23,293 | |
| | | | | | | | |
| Commitments and Contingencies | | | | | | | |
| | | | | | | | |
| Stockholders’ equity: | | | | | | | |
| Common stock, $0.0001 par value: 300,000,000 shares authorized; 54,066,165 shares issued and 53,956,380 shares outstanding at June 30, 2021 and 45,917,084 shares issued and 45,614,807 shares outstanding at December 31, 2020 | | | 5 | | | 4 | |
| Additional paid-in capital | | | 660,457 | | | 475,617 | |
| Accumulated other comprehensive income (loss) | | | 19 | | | (12) | |
| Accumulated deficit | | | (258,212) | | | (170,895) | |
| Total stockholders’ equity | | | 402,269 | | | 304,714 | |
| Total liabilities and stockholders’ equity | | $ | 439,525 | | $ | 328,007 | |
Passage Bio, Inc.
Statements of Operations and Comprehensive Loss
(Unaudited)
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|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| | **** | Three Months Ended June 30, | **** | Six Months Ended June 30, | |||||||||
| (in thousands, except share and per share data) | | 2021 | 2020 | 2021 | 2020 | | |||||||
| Operating expenses: | | | | | | | | | | | | | |
| Research and development | | $ | 33,112 | | $ | 19,902 | | $ | 58,082 | | $ | 33,019 | |
| Acquired in-process research and development | | | — | | | — | | | 1,500 | | | — | |
| General and administrative | | | 15,422 | | | 7,402 | | | 27,886 | | | 12,197 | |
| Loss from operations | | | (48,534) | | | (27,304) | | | (87,468) | | | (45,216) | |
| Interest income, net | | | 99 | | | 132 | | | 151 | | | 459 | |
| Net loss | | $ | (48,435) | | $ | (27,172) | | $ | (87,317) | | $ | (44,757) | |
| Per share information: | | | | | | | | | | | | | |
| Net loss per share of common stock, basic and diluted | | $ | (0.90) | | $ | (0.60) | | $ | (1.66) | | $ | (1.42) | |
| Weighted average common shares outstanding, basic and diluted | | | 53,885,651 | | | 45,386,308 | | | 52,615,606 | | | 31,581,851 | |
| Comprehensive loss: | | | | | | | | | | | | | |
| Net loss | | $ | (48,435) | | $ | (27,172) | | $ | (87,317) | | $ | (44,757) | |
| Unrealized gain on marketable securities | | | 26 | | | — | | | 31 | | | — | |
| Comprehensive loss | | $ | (48,409) | | $ | (27,172) | | $ | (87,286) | | $ | (44,757) | |
Exhibit 99.2
| Fulfilling the Promise of Genetic Medicines for Central Nervous System Disorders Corporate Presentation August 2021 NASDAQ GS: PASG |
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| Forward-Looking Statement This presentation includes “forward-looking statements” within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectation about timing and execution of anticipated milestones, including our planned initiation of clinical trials and the availability of clinical data from such trials; our expectations about our collaborators’ and partners’ ability to execute key initiatives; estimates regarding our cash forecasts; the expected impact of the COVID-19 pandemic on our operations; and the ability of our lead product candidates to treat their respective target CNS disorders. These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “might,” “plan,” “potential,” “possible,” “will,” “would,” and other words and terms of similar meaning. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop, obtain regulatory approval for and commercialize PBGM01, PBFT02, PBKR03 and future product candidates; the timing and results of preclinical studies and clinical trials; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; failure to protect and enforce our intellectual property, and other proprietary rights; failure to successfully execute or realize the anticipated benefits of our strategic and growth initiatives; risks relating to technology failures or breaches; our dependence on collaborators and other third parties for the development of product candidates and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; risks associated with current and potential future healthcare reforms; risks relating to attracting and retaining key personnel; failure to comply with legal and regulatory requirements; risks relating to access to capital and credit markets; and the other risks and uncertainties that are described in the Risk Factors section of our most recent filings with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this presentation. We do not undertake any obligation to publicly update any forward-looking statements except as required by law. By attending or receiving this presentation you acknowledge that you are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date such statements are made; you will be solely responsible for your own assessment of the market and our market position; and that you will conduct your own analysis and be solely responsible for forming your own view of the potential future performance of Passage Bio. |
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| Passage Bio Overview Committed to serving patients with rare and large CNS diseases OUR VISION: To fulfill the promise of genetic medicines by developing groundbreaking therapies that transform the lives of patients with CNS diseases Significant unmet medical need with few treatment options Infants and adults with severe clinical manifestations and shortened survival Rare CNS disorders (e.g., GM1 gangliosidosis, Krabbe Disease and Frontotemporal Dementia) Large CNS diseases (e.g., Alzheimer’s Disease and Temporal Lobe Epilepsy) |
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| The Passage Bio Advantage PENN GTP PARTNERSHIP Led by renowned innovator James M. Wilson, MD, PhD Access to cutting-edge research and development & next-generation technologies CNS disorders affecting both rare and large populations BROAD AND ROBUST PIPELINE 17 total program license options 3 clinical-stage therapies 4 research-stage pipeline candidates Exploratory research programs in Alzheimer’s Disease & TLE WELL-POSITIONED CORPORATE FOUNDATION Robust financial position Leaders in pediatric and adult neurodegenerative disease therapy development Deep experience in gene therapy manufacturing INTEGRATED MANUFACTURING SUPPLY CHAIN Flexible, scalable Dedicated CGMP suite Internal CMC analytics and assay infrastructure State-of-the-art technology Corporate model designed for success |
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| Passage Bio’s Differentiated Path for Clinical Success GTP expertise and insights into R&D Optimization of delivery approaches Disease-specific existing and novel capsid selection Integration of next-generation research advances Patient need Optimal capsid, transgene and promoter Preclinical safety and efficacy data Availability of measurable, predictive biomarkers Direct delivery to CNS PIPELINE WITH HIGHER PROBABILITY OF TECHNICAL AND REGULATORY SUCCESS RIGOROUS PRODUCT CANDIDATE SELECTION 17 program license options from GTP focused on CNS disorders |
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| A Broad and Robust Pipeline with Global Rights *10 additional CNS pipeline license options. † Program includes ongoing natural history study of infantile and juvenile GM1 gangliosidosis patients Transformative therapies for CNS disorders across rare and large patient populations Program* Indication Gene Discovery Pre-clinical Phase 1/2 Pivotal PEDIATRIC PBGM01† GM1 gangliosidosis GLB1 PBKR03 Krabbe disease GALC PBML04 Metachromatic leukodystrophy ARSA PBCM06 Charcot-Marie-Tooth neuropathy type 2a MFN2 ADULT PBFT02 Frontotemporal dementia GRN PBAL05 Amyotrophic lateral sclerosis C9orf72 Unnamed CNS Undisclosed Unnamed Alzheimer’s disease Target ID Unnamed Temporal lobe epilepsy Target ID |
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| Intra-Cisterna Magna (ICM) Administration Directly deliver vector into the CSF via a single injection to reach both CNS and peripheral tissues* Allows for broad CNS biodistribution Lower doses compared to IV systemic delivery Reduced impact of neutralizing antibodies Administered under anesthesia using modern neuroimaging to allow for precise delivery Currently being used in several clinical studies in both pediatric and adult populations Cisterna magna *Based on pre-clinical studies: data on file Utilized across three clinical-stage programs to directly target CNS |
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| Pathway to Patient Identification and Trial Recruitment Screening / Diagnosis Sponsoring ScreenPlus Pilot Program GM1 included in the New York newborn screening pilot program led by Dr. Melissa Wasserstein Supporting Invitae Detect LSD and InformedDNA Programs Free genetic testing and counseling offered to support earlier diagnosis and patient identification Clinical trial information provided to clinicians and patients Patient and Caregiver Activities Implementing caregiver and physician support and/or training programs Decreasing patient and site trial burden Remote visits and video capture implemented for relevant endpoints Clincierge offered for travel and accommodation support Patient Recruitment and Advocacy Strategies Maintaining strong relationships with trial sites, study coordinators and investigators Establishing clinical trial sites at centers of excellence globally Increasing clinical trial awareness Partnering with patient advocacy groups, medical specialists and organizations |
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| PBGM01 GM1 Gangliosidosis |
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| GM1 Gangliosidosis: A Devastating Pediatric Disease FATAL, PEDIATRIC NEUROLOGICAL LYSOSOMAL STORAGE DISORDER caused by GLB1 gene mutations characterized by destruction of neurons in the brain and spinal cord. Characterized by rapidly progressive neurological decline resulting in reduced muscle tone, progressive CNS dysfunction, deafness, blindness, rigidity and skeletal dysplasia. RARE AND UNDERSERVED populations with incidence of up to ~1 per 100,000 live births worldwide. No disease-modifying therapies are presently approved. Source: NIH, CHOP, American Journal of Neuroradiology |
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| PBGM01 Next-generation, proprietary AAVhu68 capsid delivers functional GLB1 gene encoding β-gal to the brain and peripheral tissues Compelling preclinical data showing meaningful transduction of both central nervous system and critical peripheral organs Received multiple global regulatory clearances for Phase 1/2 clinical trial Received Orphan Drug, Rare Pediatric Disease and Fast Track designations by FDA and Orphan designation by EC Initial safety and 30-day biomarker data from cohort 1 planned for 4Q21 Potential transformative therapy for rare, underserved disorder |
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| PBGM01: Supportive Preclinical Findings Dose-related improvements in neurological function demonstrated Top two doses similar to GLB +/- vehicle Treated mice demonstrated increased survival at all doses tested Top 2 doses achieved 100% survival to study endpoint Source: Source: Hinderer et. al, Human Gene Therapy. 2020 Nov; 31(21-22):1169–1177 Dose-Related Effect on Survival GLB1 -/- (KO) GLB1 +/- (HET) Dose 4 (highest) Dose 3 Dose 2 Dose 1 (lowest) Vehicle Vehicle Percent Survival 0 Day 100 200 300 0 50 100 Preservation of Neurological Function 240 180 120 60 0 Neurological Examinations GLB1 -/- (KO) GLB1 +/- (HET) Dose 4 (highest) Dose 3 Dose 2 Dose 1 (lowest) Vehicle Vehicle Improvement in neurological function and survival in knock-out mouse model Preclinical studies also showed increased β-gal enzyme activity and improved pathophysiology |
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| Goal of Imagine-1 Trial in Early and Late Infantile GM1 GM1 Gangliosidosis is a Continuum Disease Severity Residual Enzyme Activity Imagine-1 Trial will include Type I (Early Infantile) and Type IIa (Late Infantile) patients Negligible to 5% ~ 1– 5% ~ 3 – 10% Type I (Early Infantile) Onset <6 months Hypotonia Neurodegeneration Developmental regression Seizures Skeletal dysplasia Survival: <2 years without supportive care Type IIa (Late-Infantile) Onset 6–24 months Developmental plateau, followed by regression Impaired ambulation Impaired cognition Seizures Survival: 5 to 10 years Type II (Juvenile) Onset 2–5 years Impaired ambulation Dysarthria Variable skeletal disease Decreased cognition Survival into 2nd decade Adapted from Regier DS, et al. 2016 GLB-1 Disorders, In Adam MP, et al. GeneReviews. Elevate β-gal activity to preserve neurological function and improve clinical outcomes |
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| Imagine-1: Global Phase 1/2 Trial with PBGM01 Trial Design Phase 1/2, multi-center, open-label, single-arm, 2+2 dose escalation and confirmatory study Separate cohorts of pediatric subjects with Late Onset Infantile GM1 in cohorts 1 and 2 and Early Onset Infantile GM1 in cohorts 3 and 4 Intervention Single ICM dose of AAVhu68.hGLB1 First Read Out Initial safety and 30-day biomarker data from cohort 1 planned for 4Q21 Duration Two years, with rollover into a separate long-term follow-up study Primary Endpoints Safety and tolerability Efficacy COHORT 4 Early Infantile n = 2 DOSE 2 DOSE 1 Expansion Cohort Early Infantile n = 6 Expansion Cohort Late Infantile n = 6 COHORT 2 Late Infantile n = 2 COHORT 3 Early Infantile n = 2 COHORT 1 Late Infantile n = 2 IDMC review 60 days between subject enrollment Initial safety and biomarker data expected 4Q21 |
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| PBKR03 Krabbe Disease |
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| Krabbe Disease: A Devastating Pediatric Disease Source: NIH, CHOP, American Journal of Neuroradiology, Third Party Research FATAL, PEDIATRIC NEUROLOGICAL LYSOSOMAL STORAGE DISORDER caused by GALC gene mutations characterized by demyelination of neurons in the brain and periphery. Disease progression is rapid and highly predictable including loss of acquired milestones, staring episodes, peripheral neuropathy, seizures, blindness and deafness. RARE AND UNDERSERVED populations with incidence of up to ~2.6 per 100,000 live births worldwide. No disease-modifying therapies are presently approved. |
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| PBKR03 Next-generation, proprietary AAVhu68 capsid delivers functional GALC gene encoding galactosylceramidase (GALC) to the brain and peripheral tissues PBKR03-treated Krabbe dogs had improved central and peripheral myelination, reduced neuroinflammation and increased survival rates with full phenotypic recovery Received regulatory clearances from FDA, MHRA (UK) and Health Canada for global Phase 1/2 clinical trial Received Orphan Drug, Rare Pediatric Disease and Fast Track designations by FDA and Orphan designation by EC Clinical trial initiation expected in 3Q21 Potential transformative therapy for rare, underserved disorder |
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| PBKR03: Disease Model Data — Twitcher Mouse and Dog Models Twitcher Mouse Model: Increased GALC activity in brain, liver and serum AAV treated twitcher mouse showed clinical scores comparable to wt mice Canine Model: Increased GALC activity in CSF Decreased psychosine levels in CSF GALC Increase in Brain and Periphery PBKR03 PBKR03 GALC and Psychosine Normalization CSF Psychosine Levels (70 days post-treatment) ng/ml Meaningful brain and peripheral transduction with improved pathophysiology and function 200 240 280 320 WT (untreated) AAV-treated (6M post- treatment) FU / 10 µl CSF CSF GALC Activity (6M post - treatment) 0 0.5 1 1.5 2 Vehicle-treated AAV-treated |
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| PBKR03: Supported by Data From Canine Disease Model Naturally occurring Krabbe Dog model study showed substantial benefit with AAV treatment, including full phenotypic recovery and increased survival Survival Extended by AAV Treatment Euthanized due to disease progression Euthanized as planned per protocol Euthanized for seizure (K937) and weight loss (K993) Myelination Improvement in CNS and PNS Brain Peripheral Nerves Animal ID Average Severity Score (Grade 1-4) Vehicle AAV WT Vehicle AAV All AAV-treated dogs had improvement in CNS and peripheral nerve myelination compared to sham-treated controls, with nerve conduction velocities comparable to wild type dogs (data not shown), supporting the advancement of PBKR03 into clinical trial development. 0 20 40 60 80 K948 K930 K938 K939 K937 K933 Weeks |
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| COHORT 2 4m to <9m n = 3 COHORT 3 >1 to <4m n = 3 COHORT 1 >4m to <9m n = 3 GALax-C Global Phase 1/2 Trial with PBKR03 Trial Design Phase 1/2, multi-center, open-label, single-arm, dose-escalation and confirmatory study of PBKR03 in patients with early infantile Krabbe disease who are >1 to 9 months of age at enrollment Separate dose escalation cohorts based on age at enrollment Dosing initially in subjects >4 to <9 months of age, with initiation of dosing in subjects >1 to 4 months of age gated by safety in cohort 1 Intervention Single ICM dose of AAVhu68.CB7.CI.hGALCco.rBG (PBKR03) First Read Out Initial safety and 30-day biomarker data from cohort 1 planned for 1H22 Duration 2 years; with additional 3 years of follow-up for safety and durability of effect Primary Endpoints Safety and tolerability Efficacy IDMC review Confirmatory Cohort >1 to <4m n = 6 Confirmatory Cohort 4m to <9m n = 6 COHORT 4 >1 to <4m n = 3 DOSE 2 DOSE 1 60 days between subject enrollment First patient enrollment expected in 3Q21 |
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| PBFT02 Frontotemporal Dementia — GRN |
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| FTD-GRN: A Devastating Adult Disease DEVASTATING FORM OF DEMENTIA caused by a GRN gene mutation resulting in progranulin (PGRN) deficiency. Approximately 5–10% of FTD is caused by a GRN mutation. Disease progression is rapid and degenerative including loss of speech, loss of expression, severe behavioral changes and immobility. RARE AND UNDERSERVED populations with estimated U.S. prevalence of ~3,000 to 6,000 patients. No disease-modifying therapies are presently approved. |
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| PBFT02 Proprietary AAV1 capsid delivers function GRN gene encoding progranulin PBFT02 demonstrated increases in CSF PGRN concentrations in NHP studies to >50-fold normal human CSF PGRN concentrations Received regulatory clearances from FDA and Health Canada for global Phase 1/2 clinical trial Received Orphan Drug and Fast Track designations by FDA and Orphan designation by EC Clinical trial initiation expected in 3Q21 Potential transformative therapy for rare, underserved disorder |
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| PBFT02: Biomarker Improvement Across Brain Regions *** * Lipofuscin Accumulation Stopped in Thalamus Hexosaminidase Activity Normalization in Cortex Reduced CD68 in Hippocampus Lipofuscin accumulation is implicated in various neurodegenerative conditions Treatment stopped lipofuscin accumulation across brain regions Hexosaminidase activity is upregulated in setting of lysosomal dysfunction Treatment reduced enzyme activity at the highest dose CD68 is a lysosomal protein expressed by macrophages and activated microglia with increases reflecting higher inflammation Treatment reduced CD68 levels across brain regions Source: Hinderer et. al, Annals of Clinical and Translational Neurology. 2020 Oct; 7(10):1843–1853 PBFT02 high dose vs. vehicle in GRN-/- mice; post baseline data is 90 days post-dose * = p< 0.05*** = p<0.001 Decreases markers of lysosomal function and microgliosis 0% 20% 40% 60% 80% 100% 120% Baseline Vehicle PBFT02 0 0.2 0.4 0.6 0.8 1 1.2 Baseline Vehicle PBFT02 |
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| PBFT02: Supportive NHP Preclinical Studies Utilizing ICM A single administration of PBFT02 to NHPs via the optimized AAV1-GRN vector demonstrated transduction broadly across the brain, including a very high transduction of ependymal cells that line the ventricles of the brain and are involved with CSF production, resulting in CSF progranulin levels of more than 50-fold normal. Source: Hinderer et. al, Annals of Clinical and Translational Neurology. 2020 Oct; 7(10):1843–1853 PBFT02 Showed Dose-Related Increase in CSF PGRN at 14d PD Production of Human PGRN in CSF AAVhu68 AAVhu68 (v2) AAV5 AAV1 Normal LLOQ AAV1 Vector Expressing GFP 48% transduction of the ependymal cells in the animals treated with AAV1 |
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| upliFT-D: Global Phase 1/2 Trial with PBFT02 Trial Design Phase 1/2, multicenter, open-label, single-arm, dose escalation study of PBFT02 in early symptomatic adult subjects with frontotemporal dementia and mutations in the progranulin gene Intervention Single ICM dose of AAVh1.hPGRN (PBFT02) First Read Out Initial safety and 30-day biomarker data from cohort 1 planned for 1H22 Duration 2 years; with additional 3 years of follow-up for safety and durability of effect Primary Endpoints Safety and tolerability Efficacy OPTIONAL DOSE 3 DOSE 2 DOSE 1 60 days between subject enrollment COHORT 1 n = 3 COHORT 2 n = 3 OPTIONAL COHORT 3 n = 3 IDMC review First patient enrollment expected in 3Q21 |
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| State-of-the-Art Manufacturing |
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| Manufacturing That is Dedicated, Flexible, and Scalable In-House CMC Capabilities Princeton West CMC laboratory with state-of-the-art technologies open for analytical and process development, clinical product testing, and clinical and biomarker assay development End-to-End Supply Chain Establishing manufacturing and global distribution from clinical development through initial commercialization Dedicated Manufacturing Suite Partnership with gene therapy manufacturing leader Catalent facilitates flexible and scalable capacity Qualified CGMP suite dedicated to Passage Bio is completed and manufacturing initiated |
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| Corporate Foundation SOURCE: www.brandywinerealty.com |
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| Financial Summary * Cash, cash equivalents and marketable securities Cash balance of $408M at 6/30/21* Cash on hand to fund operations for at least 24 months Runway to potentially deliver meaningful catalysts over multiple programs |
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| Anticipated Upcoming Milestones Phase 1/2 trial for PBGM01 in patients with infantile GM1 in 1Q21 INITIATE Phase 1/2 trial for PBFT02 in patients with FTD-GRN in 3Q21 INITIATE Advance programs for MLD, ALS, CMT2A, and undisclosed adult indication Advance target ID research programs for Alzheimer’s Disease and TLE ADVANCE Evaluate and expand pipeline by pursuing new licenses in partnership with Penn’s GTP BUILD Phase 1/2 trial for PBKR03 in patients with early infantile Krabbe disease in 3Q21 INITIATE PBGM01 safety and 30-day biomarker data in 4Q21 REPORT PBFT02 safety and 30-day biomarker data in 1H22 REPORT PBKR03 safety and 30-day biomarker data in 1H22 REPORT GM1 FTD-GRN KRABBE PIPELINE ADVANCEMENT |
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| The Passage Bio Advantage PENN GTP PARTNERSHIP Led by renowned innovator James M. Wilson, MD, PhD Access to cutting-edge research and development & next-generation technologies CNS disorders affecting both rare and large populations BROAD AND ROBUST PIPELINE 17 total program license options 3 clinical-stage therapies 4 research-stage pipeline candidates Exploratory research programs in Alzheimer’s Disease & TLE WELL-POSITIONED CORPORATE FOUNDATION Robust financial position Leaders in pediatric and adult neurodegenerative disease therapy development Deep experience in gene therapy manufacturing INTEGRATED MANUFACTURING SUPPLY CHAIN Flexible, scalable Dedicated CGMP suite Internal CMC analytics and assay infrastructure State-of-the-art technology Corporate model designed for success |
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| Thank You www.passagebio.com NASDAQ GS: PASG |
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| Demonstrated Leadership LEADERSHIP TEAM BOARD OF DIRECTORS Tachi Yamada, M.D. (Chair) Frazier Athena Countouriotis, M.D. Turning Point Bruce Goldsmith, Ph.D. Passage Bio Maxine Gowen, Ph.D. Tamuro Bio Saqib Islam, J.D. SpringWorks Sandip Kapadia Harmony Biosciences Derrell Porter, M.D. Cellevolve Bio Liam Ratcliffe, M.D., Ph.D. Access Industries Tom Woiwode, Ph.D. Versant Jill M. Quigley Chief Operating Officer Eliseo Salinas, M.D. Chief R&D Officer Maria Törnsén Chief Commercial Officer Robin DeRogatis SVP Human Resources Mark Forman, M.D., Ph.D. Chief Medical Officer Chip Cale General Counsel Alex Fotopoulos Chief Technology Officer Bruce Goldsmith, Ph.D. Chief Executive Officer Deep experience in rare disease, CNS disorders and genetic medicines |
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| Cutting-Edge Gene Therapy R&D Collaboration Founded by renowned innovator and pioneer James M. Wilson, M.D., Ph.D. Chief Scientific Advisor, Passage Bio Director, Gene Therapy Program Rose H. Weiss Professor and Director, Orphan Disease Center Professor of Medicine and Pediatrics, Department of Medicine Cutting-edge research, expertise, next-generation technologies ~300 full-time employees Research contributed to successful clinical programs for approved gene therapies Glybera®, Luxturna® and Zolgensma® Supporting natural history studies and early patient identification World-class Gene Therapy Program 17 program license options for Passage Bio focused CNS disorders |
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