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):
September 22, 2022
Renovacor, Inc.
(Exact name of Registrant as Specified in Its
Charter)
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| Delaware |
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001-39271 |
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83-3169838 |
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(State or Other Jurisdiction
of Incorporation)
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(Commission
File Number)
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(IRS Employer
Identification No.)
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201 Broadway, Suite 310
Cambridge, Massachusetts
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02139 |
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Offices) |
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(Zip Code) |
Registrant’s Telephone Number, Including Area
Code: (610) 424-2650
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:
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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:
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Title of each class
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Trading
Symbol(s)
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Name of each exchange
on which registered
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| Common Stock, par value $0.0001
per share |
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RCOR |
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NYSE American LLC |
| Warrants to purchase one share
of common stock at an exercise price of $11.50 |
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RCOR.WS |
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NYSE American LLC |
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. ☐
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Item 7.01 |
Regulation FD Disclosure.
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On September 22, 2022, Renovacor, Inc. (the “Company,” or
“Renovacor”) updated information reflected in a slide presentation,
which is attached as Exhibit 99.1 to this Current Report on Form
8-K and is incorporated
herein by reference. Representatives of the Company will use the
updated presentation in various meetings from time to time.
The information furnished pursuant to Item 7.01, including Exhibit
99.1, shall not be deemed “filed” for purposes of Section 18
of the Exchange Act, or otherwise subject to the liabilities of
that section, and shall not be deemed to be incorporated by
reference in any filing under the Securities Act or Exchange Act,
except as expressly set forth by specific reference in such
filing.
Important Additional Information Regarding the Transaction Will
Be Filed With the SEC
In connection with the proposed transaction between Renovacor and
Rocket Pharmaceuticals, Inc. (“Rocket”), Renovacor and Rocket will
file relevant materials with the SEC, including a Rocket
registration statement on Form S-4 that will include a
joint proxy statement of Renovacor and Rocket and will also
constitute a prospectus of Rocket, and a definitive proxy statement
will be mailed to stockholders of Renovacor and Rocket,
respectively. INVESTORS AND SECURITY HOLDERS OF RENOVACOR AND
ROCKET ARE URGED TO READ THE PROSPECTUS/JOINT PROXY STATEMENT THAT
WILL BE INCLUDED IN THE REGISTRATION STATEMENT ON FORM S-4, AND OTHER RELEVANT
DOCUMENTS FILED OR TO BE FILED WITH THE SEC IN CONNECTION WITH THE
PROPOSED TRANSACTION OR INCORPORATED BY REFERENCE IN THE
PROSPECTUS/JOINT PROXY STATEMENT (IF ANY) CAREFULLY AND IN THEIR
ENTIRETY WHEN THEY BECOME AVAILABLE BECAUSE THEY WILL CONTAIN
IMPORTANT INFORMATION ABOUT THE PROPOSED TRANSACTION, THE PARTIES
TO THE PROPOSED TRANSACTION AND THE RISKS ASSOCIATED WITH THE
PROPOSED TRANSACTION. Investors and security holders will be able
to obtain, without charge, a copy of the registration statement,
the prospectus/joint proxy statement and other relevant documents
filed with the SEC (when available) from the SEC’s website at
http://www.sec.gov. Copies of the documents filed with
the SEC by Renovacor will be available free of charge on
Renovacor’s internet website at www.renovacor.com under
the tab “Investor & Media - Financials” or by contacting
Renovacor’s Investor Relations Department at
investors@renovacor.com. Copies of the documents filed with
the SEC by Rocket will be available free of charge on Rocket’s
internet website at www.rocketpharma.com under the tab
“Investors - SEC Filings”.
Participants in the Solicitation
Renovacor, Rocket and certain of their directors, executive
officers and other members of management may be deemed to be
participants in the solicitation of proxies with respect to the
proposed transaction. Information regarding the persons who may,
under the rules of the SEC, be deemed participants in the
solicitation of the shareholders of Renovacor or Rocket in
connection with the proposed transaction, including a description
of their direct or indirect interests, by security holdings or
otherwise, will be set forth in the prospectus/joint proxy
statement when it is filed with the SEC. Information regarding
Renovacor’s directors and executive officers is contained in
Renovacor’s definitive proxy statement, which was filed with the
SEC on April 14, 2022, and Renovacor’s Current Reports on
Form 8-K, filed
with the SEC on March 28, 2022 and June 3, 2022 (as
amended on June 24, 2022). Information regarding Rocket’s
directors and executive officers is contained in Rocket’s
definitive proxy statement, which was filed with the SEC on
April 29, 2022. Security holders and investors may obtain
additional information regarding the interests of such persons,
which may be different than those of Renovacor’s or Rocket’s
security holders generally, by reading the prospectus/joint proxy
statement and other relevant documents regarding the transaction,
which will be filed with the SEC. You may obtain these documents
(when they become available) free of charge through the website
maintained by the SEC at http://www.sec.gov and from
the Investor Relations websites of Rocket or Renovacor as described
above.
No Offer or Solicitation
This communication is not intended to and does not constitute an
offer to sell or the solicitation of an offer to subscribe for or
buy or an invitation to purchase or subscribe for any securities or
the solicitation of any vote or approval in any jurisdiction
pursuant to the proposed transaction or otherwise, nor shall there
be any sale, issuance or transfer of securities in any jurisdiction
in contravention of applicable law. This communication does not
constitute a prospectus or prospectus equivalent document. No
offering of securities shall be made except by means of a
prospectus meeting the requirements of Section 10 of the U.S.
Securities Act of 1933, as amended. In connection with the proposed
transaction, Rocket will file a registration statement on
Form S-4 that
will include a joint proxy statement of Renovacor and Rocket and
will also constitute a prospectus of Rocket. INVESTORS AND SECURITY
HOLDERS OF RENOVACOR AND ROCKET ARE URGED TO READ THE
PROSPECTUS/JOINT PROXY STATEMENT AND OTHER DOCUMENTS THAT WILL BE
FILED WITH THE SEC CAREFULLY AND IN THEIR ENTIRETY WHEN THEY BECOME
AVAILABLE BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION.
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Item 9.01 |
Financial Statements and Exhibits.
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(d) Exhibits
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Exhibit
No.
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Description |
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| 99.1 |
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Presentation of Renovacor, Inc., dated
September 22, 2022. |
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Cover Page Interactive Data File (embedded within
the Inline XBRL document) |
SIGNATURES
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 thereunto duly authorized.
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RENOVACOR, INC. |
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| Date: September 22, 2022 |
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By: |
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/s/ Magdalene Cook, M.D.
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President, Chief Executive Officer and
Director |
RENOVACOR
CORPORATE PRESENTATION NYSE: RCOR September 2022 Exhibit
99.1
Forward
Looking Statements This presentation contains forward-looking
statements within the meaning of the Private Securities Litigation
Reform Act of 1995. All statements contained in this communication
that do not relate to matters of historical fact should be
considered forward-looking statements, including statements
regarding the anticipated closing of and synergies related to the
transaction, expectations concerning market position, future
operations and other financial and operating information. These
statements are neither promises nor guarantees, but involve known
and unknown risks, uncertainties and other important factors that
may cause actual results, performance or achievements to be
materially different from any future results, performance or
achievements expressed or implied by the forward-looking
statements, including, but not limited to, the following:
uncertainties as to the timing of the consummation of the proposed
transaction with Rocket Pharmaceuticals, Inc. (“Rocket”) and the
ability of the parties to consummate the proposed transaction; the
satisfaction of the conditions precedent to consummation of the
proposed transaction, including the approval of Renovacor’s and
Rocket’s stockholders; any litigation related to the proposed
transaction; disruption of Renovacor’s or Rocket’s current plans
and operations as a result of the proposed transaction; the ability
of Renovacor or Rocket to retain and hire key personnel;
competitive responses to the proposed transaction; unexpected
costs, charges or expenses resulting from the proposed transaction;
the ability of Rocket to successfully integrate Renovacor’s
operations and technology; diversion of managements’ attention from
ongoing business operations and opportunities; the ability of
Rocket to implement its plans, forecasts and other expectations
with respect to Renovacor’s business after the completion of the
transaction and realize additional opportunities for growth and
innovation; the ability of Rocket to realize the anticipated
synergies from the proposed transaction in the anticipated amounts
or within the anticipated timeframes or costs expectations or at
all; the ability to maintain relationships with Rocket’s and
Renovacor’s respective employees, customers, other business
partners and governmental authorities; competition; the impact of
the COVID-19 pandemic on Renovacor’s and Rocket’s businesses,
supply chain and labor force; risks related to the potential impact
of general economic, political and market factors on the companies
or the proposed transaction, including as a result of inflationary
pressures; the interest from patients and families for
participation in each of Rocket’s ongoing trials, expectations
regarding the delays and impact of COVID-19 on clinical sites,
patient enrollment, trial timelines and data readouts, expectations
regarding drug supply for ongoing and anticipated trials, actions
of regulatory agencies, which may affect the initiation, timing and
progress of pre-clinical studies and clinical trials of the parties
respective product candidates; the risk that the results of
preclinical studies and clinical trials may not be predictive of
future results in connection with future studies or trials; and the
risks and uncertainties described in the “Risk Factors” section of
Renovacor’s and Rocket’s respective annual and quarterly and
reports filed the Securities Exchange Commission. These risks, as
well as other risks related to the proposed transaction, will be
included in the registration statement on Form S-4 and proxy
statement/prospectus that will be filed with the Securities and
Exchange Commission (“SEC”) in connection with the proposed
transaction. While the list of factors presented here is, and the
list of factors to be presented in the registration statement on
Form S-4 are, considered representative, no such list should be
considered to be a complete statement of all potential risks and
uncertainties. Forward-looking statements speak only as of the date
they are made. Readers are cautioned not to put undue reliance on
forward-looking statements, and neither Renovacor nor Rocket
assumes any obligation and does not intend to update or revise
these forward-looking statements, whether as a result of new
information, future events, or otherwise. Neither Renovacor nor
Rocket gives any assurance that it will achieve its expectations.
2
Rocket
Pharma to Acquire Renovacor Transaction Overview On September 19,
2022, Rocket signed a definitive agreement to acquire Renovacor in
an all-stock transaction at an exchange ratio of approximately
0.1676 (subject to adjustment based on Renovacor's net cash at
closing), an implied per-share value of $2.60, based on the volume
weighted average trading price of Rocket's common stock of $15.51
for the 30 trading days through and including the signing date RCOR
shareholders to own approximately 4.6% of Rocket immediately
following the closing Implied total equity value of approximately
$53M at close based on Renovacor’s common shares outstanding and
the acceleration and vesting of all earnout shares Transaction
preserves cash resources of the combined company and allows
Renovacor shareholders to share in future upside Transaction was
approved by the Boards of Directors of both Rocket and Renovacor,
with voting agreements in place with Renovacor's and Rocket's
directors and officers as well as certain significant shareholders
Transaction expected to close by first quarter of 2023
Mission
Renovacor’s mission is to deliver innovative precision therapies to
improve the lives of patients and families battling
genetically-driven cardiovascular and mechanistically-related
diseases Leverage the knowledge of the underlying genetic
mechanisms of disease to create transformative novel therapies
Focus near-term on BAG3 dilated cardiomyopathy (BAG3 DCM) AAV gene
therapy, which targets the underlying cause of this devastating
monogenic form of heart failure Translate advances in rare disease
populations to more prevalent populations where the unmet medical
need is high
Precision
Medicine is Changing the Treatment Paradigm for Patients and
Families with Cardiovascular Disease “Precision medicine strives to
delineate disease using multiple data sources…By defining disease
at a deeper level, we can treat patients based on an understanding
of the molecular underpinnings of their presentations, rather than
grouping patients into broad categories with one-size-fits-all
treatments.” - Dainis and Ashley 20183 Advantages of precision
medicine for heart failure (HF) Seeks to address underlying cause
to deliver greater therapeutic benefit compared to current
standard-of-care. Addressing the personal & financial burden of
multiple HF medications (avg. of ≥3/patient),1 implanted devices,
and heart transplant Expected to eliminate the need for large
patient studies2. By focusing on segments of the HF patient
population most likely to benefit Focus on endpoints that we
believe are most important to patients. Emphasizing improvements in
quality of life 1. Unlu et al, Circulation: Heart Failure. 2020 2.
Teerlink et al, NEJM 2021 3. Dainis AM, Ashley EA. JACC Basic
Transl Sci. 2018
RCSI:
retrograde coronary sinus infusion; IV: intravenous; CV:
Cardiovascular; CNS: Central nervous system DCM: Dilated
Cardiomyopathy ACM: Arrhythmogenic Cardiomyopathy Diversified
Pipeline of Programs and Therapeutic Opportunities Development in
connection with a research collaboration with the University of
Utah’s Nora Eccles Harrison Cardiovascular Research and Training
Institute. BAG3- Mediated Diseases Program Potential Indication
Research / Discovery Preclinical Phase I Phase II Phase III REN-001
(AAV9-BAG3) [RCSI] BAG3-associated DCM
AAV9-BAG3 [IV] BAG3-associated DCM AAV-BAG3
Undisclosed CV indication AAV-BAG3 Undisclosed
CNS indication AAV gene therapy
DSG2-associated ACM REN-002 (AAV gene therapy) PKP2-associated ACM
DSP-associated ACM Commercial rights held by Renovacor.
Genetic ACM As a result of the combination with Rocket, Renovacor
has suspended current guidance regarding preclinical and clinical
timelines for its programs as it evaluates these items with
Rocket
Lead
Program REN-001 for BAG3-associated Dilated Cardiomyopathy (BAG3
DCM)
Cardiovascular Disease
is the #1 Cause of Death Worldwide1 Cardiomyopathy Primary disease
of the heart muscle and a major contributor to burden of
cardiovascular disease Global mortality 370,000 in 2020 was up 43%
from 19902 Dilated Cardiomyopathy (DCM) Decrease in contractility
causes heart’s pumping chambers to enlarge Most common form of
cardiomyopathy Familial DCM 20-50% of DCM patients; up to 40% have
identifiable genetic cause2 Scientific societies recently endorsed
clinical genetic testing for DCM patients and families3,4 BAG3 DCM
Mutations in BCL2-associated athanogene 3 (BAG3) gene are among the
more common pathogenic genetic variants observed in DCM5 BAG3
expression is markedly diminished in patients with severe ischemic
or nonischemic DCM6 Currently approved therapies do not address the
underlying cause of disease 4. Musumuru K et al. Circulation:
Genomic and Precision Medicine 2020 5. Kirk JA et al. J Clin
Invest. 2021 6. Feldman AM et al. J. Cell. Physiol. 2014 Centers
for Disease Control and Prevention, Weekly Counts of Deaths by
State and Select Causes, 2019-2020 American Heart Association
Statistical Update: Heart Disease and Stroke Statistics – 2022,
mortality rate includes myocarditis Ackerman MJ et al. Heart Rhythm
2011
BAG3 DCM
is a Devastating Disease BAG3 DCM presents in otherwise healthy
individuals and rapidly progresses Caused by a genetic defect in
the BAG3 gene Cardiovascular health is dependent on adequate levels
of functional BAG3 protein BAG3 mutations typically lead to reduced
BAG3 protein levels Prevalence of BAG3 DCM in US estimated to be as
high as 30,000 patients1 and is expected to grow with increasing
genetic testing and disease awareness ~80% penetrance at >40
years of age2 At diagnosis, ~68% symptomatic, ~20% severely
symptomatic with heart failure2 Patients have significant
limitations on their activities of daily living, such as
employment, walking, attending to personal care, etc. Severely
symptomatic patients are frequently hospitalized for acute
decompensation3 High risk of progression to end stage disease ~19%
of patients with BAG3 DCM require mechanical cardiac support, heart
transplant, or have HF-related death at 12 months after diagnosis,
nearly twice the rate of similarly staged non-BAG3 DCM
patients2,4,5 Currently there are no approved therapies that
address underlying cause of disease 1. Virani et al., Circ. 2021;
Steinberg et al., Circ. 2012; Brouwers et al., Eur Heart J. 2013;
Bhambhani et al., Eur J Heart Fail. 2018; Kapoor et al., JACC:Heart
Fail. 2016; Pfeffer et al., Lancet 2003; Balmforth et al.,
JACC:Heart Fail. 2019; Felker et al., NEJM 2000; Haas et al., Eur
Heart J. 2015; Kindel et al., J Card Fail. 2012; Pugh et al., Genet
Med. 2014; Petretta et al., Am J Cardiol. 2011; McNally and
Mestroni, Circ Res. 2017; Sweet et al., Exp. Op. Orphan Drugs 2016;
Ganesh et al., Circ. 2013; Aragam et al., AHA Scient. Sess. 2021;
Villard et al., Eur. Heart J. 2011; Franaszczyk et al., J Trans
Med. 2014; Chami et al., Can J Cardiol. 2014; Arimura et al., Human
Mut. 2011; Dominguez et al., JACC 2018; Norton et al., Am J Human
Gen. 2011. 2. Domínguez et al., JACC, 2018; 3. Ahmed A. Am J
Cardiol. 2007; 4.McNamara et al., Circulation, 2001; 5. Kubanek M
et al. JACC 2013
Local
(retrograde coronary sinus infusion, or RCSI) delivery allows lower
total dose Reduces potential for various vector toxicities May
reduce burden on manufacturing We believe monogenic diseases with
well understood biology are ideal targets for AAV GTxs Targeting
disease with known genetic origin BAG3 mutations well-documented as
driver in DCM Goal is to increase BAG3 levels in DCM subjects
Non-immunogenic one-time human BAG3 payload Therapeutic payload is
human BAG3 gene DCM patients are haploinsufficient and produce low
levels of native BAG3; therefore, the protein is not foreign and
should not elicit an immune response Utilizes validated AAV9 capsid
AAV9 currently used in one approved therapy (Zolgensma) and widely
in clinical trials AAV9 has demonstrated cardiac tropism Has high
transduction efficiency Non-integrative vector We Believe
Renovacor’s REN-001 is Well Positioned for Success REN-001 is
designed to directly address the underlying cause of BAG3 DCM by
potentially increasing levels of functional BAG3 protein in the
heart GTx: gene therapy
BAG3
Regulates Multiple Important Functions in Cardiomyocytes Sources:
Knezevic et al., 2016; Myers et al., 2018 Enhances contractility by
linking the β-adrenergic receptor and L-type Ca2+ channel Cardiac
contractility Provides support for the sarcomere by linking actin
myofibrils with the Z-disc Structural support Facilitates autophagy
as a co-chaperone with heat shock proteins, recycling misfolded
proteins Protein quality control Inhibits apoptosis (programmed
cell death) through binding of BCL2 Anti-apoptosis We believe that
a gene therapy approach is best positioned to restore the broad
biological functions of BAG3 in the heart
Mutations
in BAG3 Reduce Levels of Protein and are Associated with Reduced
Force Generating Capacity in Heart Tissue from DCM Patients DCM
patient with BAG3 mutation >80% of BAG3 DCM patients had
mutations causing haploinsufficiency, resulting in reduced levels
of BAG3 protein 1 Red staining shows BAG3 protein in cardiac tissue
Healthy control 1. Domínguez et al., JACC, 2018; 2. Martin et al.,
Nature Communications, 2021 REN-001’s goal is to increase
expression of BAG3 in the heart and potentially correct the
underlying disease in BAG3 DCM patients Most BAG3 mutations in DCM
cause reduced levels of BAG3 protein Lower Higher BAG3 expression
quartiles 1st 2nd 3rd 4th * Patients with idiopathic DCM Lower
levels of BAG3 are associated with reduced contractility in DCM
patients Myofilament maximum force generating capacity (Fmax) in
DCM patient tissue * BAG3 levels in DCM patients are positively
correlated with force generating capacity 2
Sources:
Haploinsufficiency data published in Myers VD., … Feldman
AM., J Cell Physiol. 2018; AAV-BAG3 administration
adapted from data published in Myers VD., … Feldman AM., JAMA
Cardiol. 2018; and unpublished data from the Feldman lab. AAV9
BAG3 Prevents the Onset of Cardiac Impairment in a Genetic Mouse
Model of BAG3-associated DCM BAG3 protein levels Ejection fraction
~50% BAG3 protein levels seen in BAG3 +/- mice BAG3 +/- mice
develop reduced EF, recapitulating the DCM clinical phenotype
*p=.04, .01 and .003 respectively at 2, 4 and 6 weeks for +/-
AAV9-GFP vs. +/- AAV9-BAG3 arms; dose = 1×1013 genome copies (gc).
Weeks on X-axis denote time since treatment. BAG3 +/- mice: AAV9
BAG3 treatment group BAG3 +/- mice: Control group (AAV-GFP) WT
mice: AAV-GFP or AAV-BAG3 Ejection fraction in WT and BAG3 +/- mice
treated at age 6-8 weeks with AAV9-GFP or AAV9-BAG3 BAG3 +/- mice
have ~50% of BAG3 protein and develop a reduced ejection fraction
(EF) AAV9 BAG3 prevented the onset of reduced ejection
fraction
Renovacor’s Approach
to Cardiac Delivery Retrograde coronary sinus infusion (RCSI)
Overview of RCSI Coronary sinus (CS) - confluence of veins
draining heart into right atrium Routine procedure for
placement of left ventricular pacemaker leads during cardiac
resynchronization Emerging route of administration in cardiac gene
therapy studies Leverages currently used clinical
procedure and equipment Ability to transduce heart using much lower
doses of AAV Potential to maximize exposure of heart to AAV Reduced
potential for various vector toxicities Additional potential
benefits (e.g., manufacturing) REN-001 is delivered into the
coronary sinus using a catheter Potential advantages of
RCSI
RCSI
Delivery of REN-001 Resulted in Successful Cardiac Transduction
Above Key VCN Threshold at Doses <1e13 vg/kg in a Pilot Pig
Study1 Delivery of REN-001 via RCSI results in robust transduction
of a large animal heart Transcription of the BAG3 transgene
detected No safety issues detected Results informed design of
ongoing GLP-toxicology and biodistribution study in healthy pig
model VCN >1 seen in pig heart model with REN-001 doses <1e13
vg/kg Notes: Viral genome per cardiomyocyte data are shown as the
mean (+/- SEM) of 18 tissue sections taken per heart (excluding
values >3 standard deviations from the mean) and assume 8 nuclei
in each cardiomyocyte (Velayuthan et al., J Mol Cell
Cardiology, 2020); Vehicle n=1, 5e13 total vg (average of
1.46e12vg/kg) n=4, 1e14 total vg (average of 3.45e12vg/kg) n=2,
2.5e14 total vg (7.58e12vg/kg) n=1. Key Takeaways - Results
Published in JACC: BTS VCN: vector copy number REN-001 dose groups
VCN of 1 5e13 total vg; 1.46e12 vg/kg 2.5e14 total vg; 7.58e12
vg/kg 1e14 total vg; 3.45e12 vg/kg Vehicle 1. Myers et al.,
JACC:BTS, 2022
Results
Published in JACC BTS Demonstrate Diffuse Myocardial Transduction
in a Pilot Pig Study1 Notes: Mean ± SEM vector genomes per
cardiomyocyte, assuming 8 nuclei in each cardiomyocyte (Velayuthan
et al., J Mol Cell Cardiology, 2020) from five LV regions and
the RV free wall in rings 2-4 (excluding values >3 standard
deviations from the mean). # animals per group: Vehicle n=1, 5e13
total vg (average of 1.46e12 vg/kg) n=4, 1e14 total vg (average of
3.45e12 vg/kg) n=2, 2.5e14 total vg (7.58e12 vg/kg) n=1. Regional
Analysis of Transduction: Mean + SEM Vector Genomes Per
Cardiomyocyte for Rings 2, 3 and 4 Vehicle 5e13 total vg;
1.46e12 vg/kg 1e14 total vg; 3.45e12 vg/kg 2.5e14 total vg; 7.58e12
vg/kg Anterior 0.1+0.1 0.2+0.0 4.9+4.0 1.1+0.2 Anterolateral
0.0+0.0 0.2+0.1 0.6+0.4 0.8+0.3 Inferolateral 0.0+0.0 1.5+1.1
5.5+2.7 1.0+0.2 Inferior 0.0+0.0 1.6+1.2 0.6+0.1 2.9+1.8 Septum
0.0+0.0 0.6+0.5 1.0+0.2 1.1+0.2 Right ventricle 0.0+0.0 0.6+0.2
0.5+0.1 1.0+0.2 1. Myers et al., JACC:BTS, 2022
Significant Progress
Made Across Key Ongoing Preclinical Studies Natural history /
survival study of BAG3 mouse model Impaired survival phenotype
present in BAG3 DCM mouse model Preliminary / interim data
indicating LV dilation and functional decline, consistent with a
DCM phenotype New data and learnings were leveraged to optimize the
design of the dose-ranging study of REN-001 in the same mouse model
Dose-ranging and durability studies in BAG3 mouse model
Dose-ranging study optimized to assess for multiple efficacy
measures at different timepoints, leveraging emerging data from the
mouse natural history study Durability of effect study remains
underway GLP toxicology study Dosing completed in GLP toxicology
study in healthy Yucatan pigs using RCSI route of administration
LV: Left ventricle; DCM: Dilated cardiomyopathy; RCSI: Retrograde
coronary sinus infusion
Renovacor’s Mission in
Action with Lead BAG3 DCM Program Identify a condition with a high
unmet need. Global mortality from cardiomyopathy was 370,000 in
20201 Segment patients into subtypes based on the underlying cause
of their disease to enable a precision medicine approach that
has the potential to improve upon the standard-of-care Focus on a
disease subtype with a well understood monogenic origin. BAG3
DCM: Caused by reduced levels of BAG3 protein due to truncating
mutations Designed REN-001 to address the underlying cause of BAG3
DCM. Utilizes a validated AAV9 capsid to deliver a functional copy
of the BAG3 gene to cardiac cells Demonstrate preclinical POC in a
model that we believe accurately recapitulates human disease.
Prevented onset of cardiac impairment with AAV9-BAG3 in genetic
disease model of BAG3-DCM Potential successful cardiac transduction
with REN-001 delivered via RCSI at low vector dose. Local delivery
may reduce potential vector-related toxicity as well as
manufacturing burden 1. American Heart Association Statistical
Update: Heart Disease and Stroke Statistics – 2022, mortality rate
includes myocarditis; POC: Proof-of-concept
REN-001
Clinical Development Plan
Subjects
aged 18-75 with left ventricle (LV) dysfunction Depressed LVEF as
defined by AHA/ACC Guidelines NYHA Class II-III HF symptoms
Elevated NT-proBNP Genetic variant in BAG3 consistent with
haploinsufficiency Key inclusion criteria: Primary endpoint:
Secondary endpoints: LVEF: left ventricle ejection fraction; AE:
adverse event; SAE: serious adverse event; DSMB: data safety
monitoring board; NYHA; New York Heart Association Proposed Phase
I/II Clinical Study Design for REN-001 Multi-center, open-label,
single-arm dose escalation study in BAG3 DCM patients Evaluate
patients Screen Cohort 2 patients Dose Level 2 n = 3-6 Safety:
Frequency and severity of AEs and SAEs Efficacy: Cardiac function
by improvement in ejection fraction 6-minute walk test Exercise
echocardiography Kansas City Cardiomyopathy Questionnaire Serum
biomarker (NT-proBNP) Evaluate patients Patients will be enrolled
sequentially after DSMB greenlight Screen Cohort 1 patients Dose
Level 1 n = 3-6
Advancing
our Precision Therapy Pipeline New Program in genetic
Arrhythmogenic Cardiomyopathy (ACM)
ACM is a
Devastating Heart Muscle Disease Unmet Needs and Treatment
Opportunities Major unmet need for novel, precision therapy
approaches to prevent arrhythmias in ACM Current approaches to
prevent / treat arrhythmias in ACM include antiarrhythmic drugs,
catheter ablations, ICDs, and exercise restriction2 … …but these
fail to address the underlying genetics and disease biology, can be
burdensome and impact quality of life, and patients can still
experience breakthrough events2,5 ACM is a Disease of the Desmosome
Cell 1 Cell 2 Ventricular Arrhythmia in ACM Patient 3
Cardiomyopathy with a high arrhythmia burden, risk of sudden
cardiac death and, potentially, risk of heart failure development;
estimated prevalence of 1:1000-1:50001-2 Mutations in genes
encoding desmosomal proteins seen in ~50% patients1 and associated
with cardiomyocyte uncoupling, cell loss, and fibrofatty
remodeling1-3 Mean age of diagnosis: ~304-5 Precision Gene Therapy
in Development for Multiple Genetic Segments of Arrhythmogenic
Cardiomyopathy (ACM) Sources: Desmosome image adapted from Pearson;
1. Austin K, Nat Rev Cardiol. 2019; 2. Corrado D, New England
Journal of Medicine (2017); 3. Delmar M & McKenna W, Circ Res.
(2010); 4. McNally E (2017) in: Adam MP, Mirzaa GM, Pagon RA,
GeneReviews®; 5. McKenna W. Arrhythmogenic right ventricular
cardiomyopathy: diagnostic evaluation and diagnosis and treatment
and prognosis. In: UpToDate, Dardas D (Ed), UpToDate, Waltham, MA.
(Accessed on June 24, 2022).
Mutations
Causing ACM can Disrupt Gap Junctions Positive Data from Initial
Pilot Study3 Next steps: In vitro and in vivo development across
major genetic segments of ACM (PKP2, DSP, and DSG2) Restoration of
gap junction protein trafficking to the intercalated disc in a
genetic mouse model of ACM Significant reduction in premature
ventricular contractions (PVCs, hallmark proarrhythmic events seen
in ACM4) in a genetic mouse model Disease-causing mutations disrupt
gap junction protein expression at the intercalated disc;
considered to be a key driver of increased arrhythmia risk1-2
Program designed to restore gap junction protein trafficking and
reduce the arrhythmia burden in ACM Targeting the 3 largest genetic
segments of ACM (PKP2, DSP, DSG2)1-2 Precision Gene Therapy in
Development for Multiple Genetic Segments of Arrhythmogenic
Cardiomyopathy (ACM) Sources: Desmosome image adapted from Pearson;
1. Corrado D, New England Journal of Medicine (2017); 2. Austin K,
Nat Rev Cardiol. 2019; 3. Palatinus J. Circulation (2021); 4.
Gasperetti A. JAMA Cardiology (2022). Disease-causing mutations can
lower Cx43 expression at the intercalated disc
Renovacor’s Mission in
Action with New Genetic ACM Program Segment patients into subtypes
based on the underlying genetic drivers of their disease
Disease-causing mutations, most commonly in genes encoding
desmosomal proteins, can be identified in approximately half of
patients with ACM Plakophilin-2 (PKP2), desmoplakin (DSP), and
desmoglein 2 (DSG2) are the three largest genetic segments of ACM
Identify a condition with a high unmet need ACM is a genetic
disorder characterized by an increased risk of potentially
life-threatening arrhythmias, myocardial dysfunction, and
fibrofatty replacement of myocardial tissue Current treatments fail
to address the underlying genetics and disease biology Seek to
address a causal disease pathway and leverage non-invasive clinical
measurements to facilitate efficient R&D Focus on a precision
therapy approach to target underlying disease biology Design
smaller and more cost-efficient patient studies Focus on endpoints
that we believe are most important to patients Sources: 1. Austin
K, Nat Rev Cardiol. 2019; 2. Corrado D, New England Journal of
Medicine (2017); 3. Delmar M & McKenna W, Circ Res. (2010); 4.
McNally E (2017) in: Adam MP, Mirzaa GM, Pagon RA, GeneReviews®; 5.
McKenna W. Arrhythmogenic right ventricular cardiomyopathy:
Diagnostic evaluation and diagnosis and treatment and prognosis.
In: UpToDate, Dardas D (Ed), UpToDate, Waltham, MA. (Accessed on
June 24, 2022.).
BAG3
Pipeline Expansion Opportunities
BAG3
Protein Levels are also Decreased in other Forms of Heart Failure
HFrEF: Heart failure with reduced ejection fraction; Notes: *
p<0.05 between MI-GFP and Sham-GFP, and between wild-type / sham
and MLP-/- / TAC mice 1. Fang, X., et al., J Clin Invest., 2017; 2.
Renovacor, data on file (2021); 3. Feldman, AM et al., J. Cellular
Physiology, 2014 MLP-/- and TAC mouse models1 Post-MI Pig Model2 HF
Patients3 Increasing BAG3 expression has the potential to impact
additional heart failure patient populations
AAV9 BAG3
Significantly Improved the EF in a Post-MI Mouse Model1 A –
Infarction; B – Week 1 echo; C – Treatment/ control injected
retro-orbital at week 8 post-MI; D – Echo at sacrifice, 23 days
post-treatment; * p<0.0001; †p<0.0001 BAG3 protein levels
Post-MI mice have reduced BAG3 expression and AAV9 BAG3 increased
protein levels AAV9 BAG3 significantly improved the EF in post-MI
mice (1) Mice develop a HF phenotype with reduced BAG3; (2)
AAV9-BAG3 restored normal ejection fraction in post-MI mice; and
(3) AAV9-BAG3 had no impact on LVEF in control mice CLSQ:
Calsequestrin; Notes: MI: Mice randomized to receive myocardial
infarction * p<0.05 between MI-GFP and Sham-GFP; 1. Knezevic T.,
… Feldman, A.M., J Am Coll Cardiol Basic Trans Science. 2016; 1.
BAG3 has a known autoregulatory mechanism (Gentilella, A. &
Khalili, K., J Cell Biochem. 2009)
Corporate
Kumar
Dhanasekharan, PhD I Senior VP, Technical Operations 20+ years of
CMC development and manufacturing experience across complex protein
therapeutics, monoclonal antibodies and in recent years, AAV gene
therapies. Jordan Shin, MD, PhD, FACC I Senior VP, Clinical
Development and Translational Science 20+ of expertise in clinical
development, academic research and medical practice Magdalene Cook,
MD I President and CEO 20+ years of experience in the life science
industry primarily in investing, consulting and launching new
ventures; Principal, Aisling Capital and Board member of multiple
companies Matt Killeen, PhD, FACC, FHRS I CSO 15+ years of
experience, spanning cardiovascular disease research and
biotech/pharma R&D and strategy; Head of Cardiovascular
Research at BioMarin; established cardiovascular therapeutic area
and led the discovery and development of AAV-based gene therapies
for inherited heart diseases; expertise in genetic heart disease
biology and potential therapeutic opportunities Wendy DiCicco I CFO
25+ years expertise in finance, strategy, M&A as well as
executive roles in public and private companies Marc Semigran, MD I
CMO 30+ years of experience treating HF and cardiomyopathy; Senior
VP of Medical Sciences and CMO at MyoKardia; experience in
developing and designing clinical trials for novel therapies for
cardiovascular and heart failure/HFpEF Elizabeth White, PhD I CBO
and Senior VP, Operations 30+ years of biotech/pharma experience
including in strategy, business development, new product planning,
portfolio prioritization in start-ups & large companies Jiwen
Zhang, PhD I Chief Regulatory Officer 20+ years of regulatory
affairs and quality assurance experience, with >10 years
specifically in cell and gene therapy Experienced Leadership
Team
Scientific
Advisory Board Experts in Cardiovascular Disease Experts in Gene
Therapy R&D Douglas Mann, MD Lewin Prof. of Medicine, former
Director of Cardiovascular Div., Washington University School of
Medicine Past President, HFSA Lifetime Achievement Award, HFSA
Editor-in-Chief, JACC Basic Translational Science Arthur Feldman,
MD, PhD Renovacor, Founder and Chair of SAB Laura H. Carnell
Professor of Medicine, Temple Former Chief of Cardiology UPMC Past
President HFSA, Assoc. of Professors of Cardiology Lifetime
Achievement Award, HFSA; Distinguished Scientist Award ACC, 2019
Dennis McNamara, MD Professor of Medicine and Dir. of the Heart
Failure Research Center, UPMC Leading expert in the genetics of
dilated and hypertrophic cardiomyopathy National Principal
Investigator – IMAC I, II & III; GRAFH I & II Michael
Bristow, MD, PhD Professor of Medicine and former Head of
Cardiology, Univ. of Colorado Health Sciences Co-founder, President
and CEO, ARCA Biopharma Founder, Myogen Lifetime Achievement Award,
HFSA Credited with development of science and clinical utility of
b-blockers for HF Joseph Glorioso III, PhD Professor in the Dept.
of Microbiology and Molecular Genetics, UPMC Founding member and
past president of the American Society of Gene Therapy Co-founder
and Chair of Scientific Advisory Board at Oncorus, Inc. and Coda
Biotherapeutics Richard Peluso, PhD Founder and President, RWP
BioConsulting, LLC Retired Vice President of Merck Vaccines &
Biologics Bioprocess R&D Previous faculty member of
Microbiology Departments at Thomas Jefferson University, University
of Minnesota, and Mt. Sinai School of Medicine Lee Sweeney, PhD
Professor in the Dept. of Pharmacology & Therapeutics,
University of Florida College of Medicine Much of Dr. Sweeney’s
research program is translational in focus and has produced highly
cited research on inherited forms of cardiovascular disease and on
the skeletal and cardiac aspects of muscular dystrophy.
Renovacor’s mission is
to deliver innovative precision therapies to improve the lives of
patients and families battling genetically-driven cardiovascular
and mechanistically-related diseases Mission and Value Proposition
Lead BAG3 DCM program targets the underlying cause of a monogenic
disease with an AAV9-gene therapy Backed by strong institutional
investor syndicate Proof-of-concept demonstrated in multiple
preclinical models Experienced management and exceptional
scientific advisors
For
follow-up please contact: info@renovacor.com
Important
Additional Information Regarding the Transaction Will Be Filed With
the SEC In connection with the proposed transaction between
Renovacor and Rocket, Renovacor and Rocket will file relevant
materials with the SEC, including a Rocket registration statement
on Form S-4 that will include a joint proxy statement of
Renovacor and Rocket and will also constitute a prospectus of
Rocket, and a definitive proxy statement will be mailed to
stockholders of Renovacor and Rocket, respectively. INVESTORS AND
SECURITY HOLDERS OF RENOVACOR AND ROCKET ARE URGED TO READ THE
PROSPECTUS/JOINT PROXY STATEMENT THAT WILL BE INCLUDED IN THE
REGISTRATION STATEMENT ON FORM S-4, AND OTHER RELEVANT
DOCUMENTS FILED OR TO BE FILED WITH THE SEC IN CONNECTION WITH THE
PROPOSED TRANSACTION OR INCORPORATED BY REFERENCE IN THE
PROSPECTUS/JOINT PROXY STATEMENT (IF ANY) CAREFULLY AND IN THEIR
ENTIRETY WHEN THEY BECOME AVAILABLE BECAUSE THEY WILL CONTAIN
IMPORTANT INFORMATION ABOUT THE PROPOSED TRANSACTION, THE PARTIES
TO THE PROPOSED TRANSACTION AND THE RISKS ASSOCIATED WITH THE
PROPOSED TRANSACTION. Investors and security holders will be able
to obtain, without charge, a copy of the registration statement,
the prospectus/joint proxy statement and other relevant documents
filed with the SEC (when available) from the SEC’s website
at http://www.sec.gov. Copies of the documents filed with
the SEC by Renovacor will be available free of charge on
Renovacor’s internet website at www.renovacor.com under
the tab “Investor & Media - Financials” or by contacting
Renovacor’s Investor Relations Department
at investors@renovacor.com. Copies of the documents filed with
the SEC by Rocket will be available free of charge on Rocket’s
internet website at www.rocketpharma.com under the tab
“Investors – SEC Filings”. Participants in the Solicitation
Renovacor, Rocket and certain of their directors, executive
officers and other members of management may be deemed to be
participants in the solicitation of proxies with respect to the
proposed transaction. Information regarding the persons who may,
under the rules of the SEC, be deemed participants in the
solicitation of the shareholders of Renovacor or Rocket in
connection with the proposed transaction, including a description
of their direct or indirect interests, by security holdings or
otherwise, will be set forth in the prospectus/joint proxy
statement when it is filed with the SEC. Information regarding
Renovacor’s directors and executive officers is contained in
Renovacor’s definitive proxy statement, which was filed with the
SEC on April 14, 2022, and Renovacor’s Current Reports on
Form 8-K, filed with the SEC on March 28, 2022 and
June 3, 2022 (as amended on June 24, 2022). Information
regarding Rocket’s directors and executive officers is contained in
Rocket’s definitive proxy statement, which was filed with the SEC
on April 29, 2022. Security holders and investors may obtain
additional information regarding the interests of such persons,
which may be different than those of Renovacor’s or Rocket’s
security holders generally, by reading the prospectus/joint proxy
statement and other relevant documents regarding the transaction,
which will be filed with the SEC. You may obtain these documents
(when they become available) free of charge through the website
maintained by the SEC at http://www.sec.gov and from the
Investor Relations websites of Rocket or Renovacor as described
above. No Offer or Solicitation This presentation is not intended
to and does not constitute an offer to sell or the solicitation of
an offer to subscribe for or buy or an invitation to purchase or
subscribe for any securities or the solicitation of any vote or
approval in any jurisdiction pursuant to the proposed transaction
or otherwise, nor shall there be any sale, issuance or transfer of
securities in any jurisdiction in contravention of applicable law.
This presentation does not constitute a prospectus or prospectus
equivalent document. No offering of securities shall be made except
by means of a prospectus meeting the requirements of
Section 10 of the U.S. Securities Act of 1933, as amended. In
connection with the proposed transaction, Rocket will file a
registration statement on Form S-4 that will include a
joint proxy statement of Renovacor and Rocket and will also
constitute a prospectus of Rocket. INVESTORS AND SECURITY HOLDERS
OF RENOVACOR AND ROCKET ARE URGED TO READ THE PROSPECTUS/JOINT
PROXY STATEMENT AND OTHER DOCUMENTS THAT WILL BE FILED WITH THE SEC
CAREFULLY AND IN THEIR ENTIRETY WHEN THEY BECOME AVAILABLE BECAUSE
THEY WILL CONTAIN IMPORTANT INFORMATION.
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