# EDGAR Filing Document

**Accession Number:** 0001661181
**File Stem:** 0001193125-25-217810
**Filing Date:** 2025-9
**Character Count:** 32993
**Document Hash:** ed9bc683bbf199db8a71dd29fecbd2ba
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0001193125-25-217810.hdr.sgml**: 20250925

**ACCESSION NUMBER**: 0001193125-25-217810

**CONFORMED SUBMISSION TYPE**: 8-K

**PUBLIC DOCUMENT COUNT**: 15

**CONFORMED PERIOD OF REPORT**: 20250925

**ITEM INFORMATION**: Regulation FD Disclosure

**ITEM INFORMATION**: Other Events

**ITEM INFORMATION**: Financial Statements and Exhibits

**FILED AS OF DATE**: 20250925

**DATE AS OF CHANGE**: 20250925

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** Organogenesis Holdings Inc.
- **CENTRAL INDEX KEY:** 0001661181
- **STANDARD INDUSTRIAL CLASSIFICATION:** PHARMACEUTICAL PREPARATIONS [2834]
- **ORGANIZATION NAME:** 03 Life Sciences
- **EIN:** 000000000
- **STATE OF INCORPORATION:** DE
- **FISCAL YEAR END:** 1231

**FILING VALUES:**
- **FORM TYPE:** 8-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 001-37906
- **FILM NUMBER:** 251344520

**BUSINESS ADDRESS:**
- **STREET 1:** 85 DAN ROAD
- **CITY:** CANTON
- **STATE:** MA
- **ZIP:** 02021
- **BUSINESS PHONE:** 781-575-0775

**MAIL ADDRESS:**
- **STREET 1:** 85 DAN ROAD
- **CITY:** CANTON
- **STATE:** MA
- **ZIP:** 02021

**FORMER COMPANY:**
- **FORMER CONFORMED NAME:** Avista Healthcare Public Acquisition Corp.
- **DATE OF NAME CHANGE:** 20151215

?xml version='1.0' encoding='ASCII'? 8-K

### 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 25, 2025

## ORGANOGENESIS HOLDINGS INC.

#### (Exact Name of Registrant as specified in its charter)

---

| | | |
|:---|:---|:---|
| **Delaware** | **001-37906** | **98-1329150** |
| **(State or Other Jurisdiction**<br> **of Incorporation)** | **(Commission**<br> **File Number)** | **(IRS Employer**<br> **Identification No.)** |

---

---

| | |
|:---|:---|
| **85 Dan Road**<br> **Canton, MA** | **02021** |
| **(Address of principal executive offices)** | **(Zip Code)** |

---

(781) 575-0775

#### (Registrant's telephone number, including area code)

#### Not Applicable

#### (Registrant's name or former address, if change 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)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

---

| | | |
|:---|:---|:---|
| **Title of each class** | **Trading<br>Symbol(s)** | **Name of each exchange<br>on which registered** |
| Class A Common Stock, $0.0001 par value | ORGO | Nasdaq Capital 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 pursuant to Section 13(a) of the Exchange Act. ☐

------

---

| | |
|:---|:---|
| **Item 7.01** | **Regulation FD Disclosure.**  |

---

On September 25, 2025, Organogenesis Holdings Inc. (the "Company") issued a press release announcing an update on its second Phase 3 randomized controlled trial ("RCT") of ReNu, a cryopreserved amniotic suspension allograft ("ASA") for the management of symptoms associated with knee osteoarthritis ("OA"). A copy of the press release is furnished as Exhibit 99.1 hereto and is incorporated herein by this reference.

The information in Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.1 attached hereto, is intended to be furnished and shall not be deemed "filed" for purposes of Section 18 of the Securities and Exchange Act of 1934, as amended (the "Exchange Act"), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in any such filing.

---

| | |
|:---|:---|
| **Item 8.01.** | **Other Events.**  |

---

As noted in Item 7.01 above, the Company announced an update on its second Phase 3 RCT of ReNu, a cryopreserved ASA for the management of symptoms associated with knee OA on September 25, 2025.

This second Phase 3 trial was a fully enrolled 594 patient trial and was a prospective, double-blind, multicenter, saline-controlled, parallel group, RCT of ReNu ASA, for the treatment of subjects with mild to severe symptomatic knee OA. Patients were randomized to receive a single intra-articular ("IA") injection of either saline control or ReNu.

This second Phase 3 RCT of ReNu did not achieve statistical significance for its primary endpoint, despite the ReNu results demonstrating a numerical improvement in baseline pain reduction over the first Phase 3 trial. Baseline pain reduction at six months for ReNu was -6.9 for the second Phase 3 study compared to -6.0 in the first Phase 3 study. Additionally, the ReNu results continued to demonstrate a favorable safety profile.

The primary endpoint for the study was the difference between ReNu and Saline groups in the reduction in knee pain at six months assessed by the Western Ontario and McMaster Universities Arthritis Index ("WOMAC") pain scale. The study data demonstrated a numerical improvement of -0.5 favoring ReNu (p=0.0393 one-sided p-value, compared to p=0.023 target threshold). The first Phase 3 trial achieved improvement of -0.7 favoring ReNu, which was statistically significant (p=0.0177, one sided p-value, compared to p=0.023 target threshold). Additional data from the Phase 3 RCTs is included as Exhibit 99.2 and is incorporated herein by reference.

The Company plans to request a pre-Biologics License Application ("BLA") meeting with the FDA by the end of October 2025 to discuss the BLA submission pathway, including potentially using the combined efficacy analysis from both Phase 3 studies of ReNu to support a BLA approval.

#### Forward-Looking Statements
This Current Report on Form 8-K contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements relate to expectations or forecasts of future events. Forward-looking statements may be identified by the use of words such as "intend," "seek," "anticipate," "believe," "expect," "estimate," "potential" and other similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These statements concern, and these risks and uncertainties include, among others: the risks and uncertainties inherent in clinical development; the FDA may require additional evidence for ReNu before we can submit a BLA or get a BLA approved, which we may not be able to obtain; that other clinical trials of ReNu may produce different results; the likelihood and timing of possible regulatory approval and commercial launch of ReNu; determinations by regulatory and administrative governmental authorities which may delay or restrict our ability to develop or commercialize ReNu; ongoing regulatory obligations and oversight impacting ReNu; unforeseen safety issues resulting from the administration of ReNu in patients; competing products and product candidates that may be superior to our products and product candidates; uncertainty of market acceptance and commercial success of ReNu and the impact of studies (whether conducted by us or others and whether mandated or voluntary) on the commercial success of ReNu; our ability to manufacture and manage supply components for ReNu; the availability and extent of reimbursement of ReNu from third-party payers, including private payer healthcare and insurance programs and government programs such as Medicare and Medicaid; coverage and reimbursement determinations by such payers, including local coverage determinations by Medicare Part A/B Medicare Administrative Contractors; new policies and procedures adopted by such payers; unanticipated expenses; the costs of developing, producing, and selling ReNu; our ability to meet our sales or other financial projections or guidance and changes to the assumptions underlying those projections or guidance; and other risks and uncertainties described in the Company's filings with the Securities and Exchange Commission, including Item 1A (Risk Factors) of the Company's Form 10-K for the year ended December 31, 2024 and its subsequently filed periodic reports. You are cautioned not to place undue reliance upon any forward-looking statements, which speak only as of the date made. Although it may voluntarily do so from time to time, the Company undertakes no commitment to update or revise the forward-looking statements, whether as a result of new information, future events or otherwise, except as required by applicable securities laws.

------

---

| | |
|:---|:---|
| **Item 9.01.** | **Financial Statements and Exhibits.**  |

---

(d) Exhibits

---

| | |
|:---|:---|
| **Exhibit<br>No.** | **Description** |
| 99.1 | [Press Release dated September 25, 2025](d870311dex991.htm) |
| 99.2 | [Data from Phase 3 RCTs of ReNu dated September 25, 2025](d870311dex992.htm) |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) |

---

------

#### SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

---

| | |
|:---|:---|
| Organogenesis Holdings Inc. | Organogenesis Holdings Inc. |
| By: | /s/ Lori Freedman |
| Name: | Lori Freedman |
| Title: | Chief Administrative and Legal Officer |

---

Date: September 25, 2025

## Exhibit 99.1

**Exhibit 99.1**![LOGO](g870311g0926003036049.jpg)

Organogenesis Provides Update on Second Phase 3 ReNu<sup>®</sup> Study

Company maintains confidence in ReNu as innovative pain management therapy

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Second Phase 3 trial demonstrates numerical improvement in baseline pain reduction over the first Phase 3 trial
despite not meeting the primary endpoint

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Statistically significant maintenance of function (p<0.0001)

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Company will request pre-BLA meeting with FDA to discuss submission
pathway

**CANTON, Mass., September 25, 2025 (GLOBE NEWSWIRE) –** Organogenesis Holdings Inc. (Nasdaq: ORGO), a leading regenerative medicine company focused on the development, manufacture and commercialization of product solutions for the Advanced Wound Care and Surgical and Sports Medicine markets, today announced that the second Phase 3 randomized controlled trial (RCT) of ReNu, a cryopreserved amniotic suspension allograft (ASA) for the management of symptoms associated with knee osteoarthritis (OA), did not achieve statistical significance for its primary endpoint, despite the ReNu results demonstrating a numerical improvement in baseline pain reduction over the first Phase 3 trial. Baseline pain reduction at six months for ReNu was -6.9 for the second Phase 3 study compared to -6.0 in the first Phase 3 study. Additionally, the ReNu results continued to demonstrate a favorable safety profile.

The primary endpoint for the study is the difference between ReNu and Saline groups in the reduction in knee pain at six months assessed by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scale. The study demonstrated a numerical improvement of -0.5<sup>1</sup> favoring ReNu (p=0.0393 one-sided p-value, compared to p=0.023 target threshold). The first Phase 3 trial achieved improvement of -0.7<sup>2</sup> favoring ReNu, which was statistically significant (p=0.0177, one sided p-value, compared to p=0.023 target threshold).

"Given the first Phase 3 trial achieved a statistically significant reduction in pain compared to Saline and the second Phase 3 trial demonstrated a numerical improvement in baseline pain reduction over the first Phase 3, we believe these results support the potential approval of ReNu for pain symptoms associated with knee OA, including those patients classified as most severe," said Patrick Bilbo, Chief Operating Officer of Organogenesis. "As a next step, we will request a pre-BLA meeting with the FDA by the end of October to discuss the submission pathway, including using the combined efficacy analysis from both Phase 3 studies to support a BLA approval."

<sup>1</sup> Second Phase 3 Reduction in baseline knee pain at six months assessed by WOMAC pain scale: ReNu -6.9 & Saline -6.4

<sup>2</sup> First Phase 3 Reduction in baseline knee pain at six months assessed by WOMAC pain scale: ReNu -6.0 & Saline -5.3

------

ReNu has now been studied in three large RCTs of more than 1,300 patients combined. Organogenesis believes the totality of this data is compelling evidence for the FDA to review in a Biologics License Application (BLA). Additionally, the FDA granted ReNu Regenerative Medicine Advanced Therapy (RMAT) designation based on ReNu demonstrating the potential to treat an unmet medical need related to a serious condition.

"The results for ReNu support our continued confidence in the potential of ReNu as an innovative pain management product," said Gary S. Gillheeney, Sr., President, Chief Executive Officer and Chair of the Board for Organogenesis. "We believe ReNu, if approved, will address a significant unmet medical need for the millions of Americans suffering from symptomatic knee OA."

Knee OA is a degenerative joint disease that is estimated to affect more than 30 million Americans. It is ranked among the most common causes of disability and poor quality of life, generally characterized by pain and functionality deficits. End stage management of the disease in these patients is typically a total knee replacement when all other treatment options are exhausted.

The fully enrolled 594 patient second Phase 3 trial is a prospective, double-blind, multicenter, saline-controlled, parallel group, RCT of ReNu ASA, for the treatment of subjects with mild to severe symptomatic knee OA. Patients were randomized to receive a single intra-articular (IA) injection of either saline control or ReNu.

Additional top-line data tables from both Phase 3 studies are available in a Current Report on Form 8-K, which the Company filed today with the SEC and can be found at SEC.gov.

**About ReNu<sup>®</sup>**

ReNu is a cryopreserved, amniotic suspension allograft (ASA) developed for the management of symptomatic knee osteoarthritis. ReNu consists of amniotic fluid cells and micronized amniotic membrane and contains cellular, growth factor, and extracellular matrix components. ReNu received FDA Regenerative Medicine Advanced Therapy (RMAT) designation for Knee OA in 2021.

**About Organogenesis Holdings Inc.**

Organogenesis Holdings Inc. is a leading regenerative medicine company focused on the development, manufacture, and commercialization of solutions for the advanced wound care and surgical and sports medicine markets. Organogenesis offers a comprehensive portfolio of innovative regenerative products to address patient needs across the continuum of care. For more information, visit <u>www.organogenesis.com</u>.

------

**Forward-Looking Statements** 

This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements relate to expectations or forecasts of future events. Forward-looking statements may be identified by the use of words such as "intend," "seek," "anticipate," "believe," "expect," "estimate," "potential" and other similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These statements concern, and these risks and uncertainties include, among others: the risks and uncertainties inherent in clinical development; the FDA may require additional evidence for ReNu before we can submit a BLA or get a BLA approved, which we may not be able to obtain; that other clinical trials of ReNu may produce different results; the likelihood and timing of possible regulatory approval and commercial launch of ReNu; determinations by regulatory and administrative governmental authorities which may delay or restrict our ability to develop or commercialize ReNu; ongoing regulatory obligations and oversight impacting ReNu; unforeseen safety issues resulting from the administration of ReNu in patients; competing products and product candidates that may be superior to our products and product candidates; uncertainty of market acceptance and commercial success of ReNu and the impact of studies (whether conducted by us or others and whether mandated or voluntary) on the commercial success of ReNu; our ability to manufacture and manage supply components for ReNu; the availability and extent of reimbursement of ReNu from third-party payers, including private payer healthcare and insurance programs and government programs such as Medicare and Medicaid; coverage and reimbursement determinations by such payers, including local coverage determinations by Medicare Part A/B Medicare Administrative Contractors; new policies and procedures adopted by such payers; unanticipated expenses; the costs of developing, producing, and selling ReNu; our ability to meet our sales or other financial projections or guidance and changes to the assumptions underlying those projections or guidance; and other risks and uncertainties described in the Company's filings with the Securities and Exchange Commission, including Item 1A (Risk Factors) of the Company's Form 10-K for the year ended December 31, 2024 and its subsequently filed periodic reports. You are cautioned not to place undue reliance upon any forward-looking statements, which speak only as of the date made. Although it may voluntarily do so from time to time, the Company undertakes no commitment to update or revise the forward-looking statements, whether as a result of new information, future events or otherwise, except as required by applicable securities laws.

Investor Inquiries: ICR Healthcare Mike Piccinino, CFA <u>OrganoIR@westwicke.com</u>

Press and Media Inquiries: Organogenesis <u>Communications@organo.com</u>

## Exhibit 99.2

**Exhibit 99.2** 

Organogenesis 22OA (Second Phase 3 ReNu Study)

Table 14.2.1.1

Change from Baseline WOMAC Pain Scale at 6 Months - Control-based Mean Imputation

FAS Population

---

| | | |
|:---|:---|:---|
| Statistics | ASA<br>(N = 296) | Placebo<br>(N = 298) |
|  WOMAC Pain Scale |  |  |
|  Change from Baseline to Week 26 |  |  |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; n | 244 | 252 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Mean (SD) | -7.0 (4.55) | -6.5 (4.89) |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Median | -7.0 | -6.0 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Q1, Q3 | -11.0, -4.0 | -10.0, -3.0 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Min, Max | -20, 4 | -20, 6 |
|  Number of subjects With missing data | 52 (17.6%) | 46 (15.4%) |
|  CFB LS Mean Estimate | -6.9 | -6.4 |
|  Standard Error | 0.22 | 0.25 |
|  CFB LS Mean Difference (ASA - Placebo) | -0.5 |  |
|  One-sided 97.7% CI of CFB LS Mean Difference | [-Inf to 0.072] |  |
|  p-value | 0.0393 |  |

---

Abbreviations: ASA = Amniotic Suspension Allograft; CFB = Change from Baseline; CI = Confidence Interval; FAS = Full Analysis Set; Inf = Infinity; KL = Kellgren-Lawrence; LS = Least Squares; Max = Maximum; Min *=* Minimum; MMRM = Mixed-Effects Model Repeated Measures; Q1 = First Quartile; Q3 = Third Quartile; SD = Standard Deviation; WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index. Baseline is defined as the last non-missing measurement preceding the single injection (ASA or placebo). Negative change from baseline indicates better health.

Subjects with intercurrent events, i.e., those who used prohibited medications (except protocol permitted Paracetamol) or who had knee replacement surgery on the index knee will be considered with missing data at visits occurring after the earliest of these intercurrent events.

A control-based mean imputation is used to handle missing data (Mehrotra et.al. 2017). A separate MMRM model is fitted per group using baseline WOMAC Pain Score value and KL grade as covariates. Estimation of the group LS means is done by setting the covariates equal to the pooled (ASA + Placebo) means. Visits included in the MMRM are Week 1, Week 6, Week 12, Week 18, and Week 26 with visit included as a fixed factor and baseline-by-visit as an interaction term. Unstructured covariance is used to model within-subject errors and Kenward-Roger approximation is used to estimate denominator degrees of freedom and adjust standard errors.

p-value is derived from a t-test 1-sided at alpha level 0.023.

Source: Listing 16.2.6.1.

------

Organogenesis 22OA (Second Phase 3 ReNu Study)

Table 14.2.2 .1.1

Change from Baseline WOMAC Function Scale at 6 Months - Control-based Mean Imputation

FAS Population

---

| | | |
|:---|:---|:---|
| Statistics | ASA<br>(N = 296) | Placebo<br>(N =298) |
|  WOMAC Function Scale |  |  |
|  Change from Baseline to Week 26 |  |  |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; n | 244 | 252 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Mean (SD) | -21.0 (15.73) | -20.3 (15.87) |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Median | -20.0 | -17.0 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Q1, Q3 | -33.0, -9.0 | -32.0, -8.5 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Min, Max | -67, 16 | -68, 14 |
|  Number of subjects with missing data | 52 (17.6%) | 46 (15.4%) |
|  CFB LS Mean Estimate | -21.1 | -19.6 |
|  Standard Error | 0.76 | 0.80 |
|  CFB LS Mean Difference (ASA- Placebo) | -1.5 |  |
|  95% CI of CFB LS Mean Difference | [-3.430 to 0.494] |  |
|  p-value | <.0001 |  |

---

Abbreviations: ASA = Amniotic Suspension Allograft; CFB = Change from Baseline; CI = Confidence Interval; FAS = Full Analysis Set; KL = Kellgren-Lawrence; LS = least squares; Max = Maximum; Min = Minimum; MMRM = Mixed-Effects Model Repeated Measures; Q1 = First Quartile; Q3 = Third Quartile; SD = Standard deviation; WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index. Baseline is defined as the last non-missing measurement preceding the single injection (ASA or placebo). Negative change from baseline indicates better health.

Subjects with intercurrent events, i.e., those who used prohibited medications (except protocol permitted Paracetamol) or who had knee replacement surgery on the index knee will be considered with missing data at visits occurring after the ear1iest of these intercurrent events.

A control-based mean imputation is used to handle missing data (Mehrotra et.al. 2017). A separate Mixed-Effects Model Repeated Measures (MMRM) model is fitted per group using the baseline WOMAC Function Score value and KL grade as covariates. Estimation of the group LS means is done by setting the covariates equal to the pooled (ASA + Placebo) means. Visits included in the MMRM are Week 1, Week 6, Week 12, Week 18, and Week 26 with visit included as a fixed factor and baseline-by-visit as an interaction term. Unstructured covariance is used to model within-subject errors and Kenward-Roger approximation used to estimate denominator degrees of freedom and adjust standard errors.

Test of non-inferiority with a margin or + 7 points. p-value is derived from a t-test one-sided at alpha level 0.025.

Source: Listing 16.2.6.1.

------

Organogenesis 22OA (Second Phase 3 ReNu Study)

Table 14.3.1.1

Overall Summary of Treatment Emergent Adverse Events

Safety Population

---

| | | | |
|:---|:---|:---|:---|
|  | ASA | Placebo | Total |
|  | (N = 293) | (N = 297) | (N = 590) |
| <u>Subjects with at Least One Treatment Emergent:</u> | (PM = 3376.72) | (PM = 3365.22) | (PM = 6741.95) |
|  Adverse Event | 123 (42.0%) | 122 (41.1%) | 245 (41.5%) |
|  Adverse Event Categorized as Mild | 82 (28.0%) | 87 (29.3%) | 169 (28.6%) |
|  Adverse Event Categorized as Moderate | 80 (27.3%) | 68 (22.9%) | 148 (25.1%) |
|  Adverse Event Categorized as Severe | 8 (2.7%) | 19 (6.4%) | 27 (4.6%) |
|  Adverse Event Categorized as Life Threatening | 0 | 0 | 0 |
|  Adverse Event Related to Study Drug | 23 (7.8%) | 12 (4.0%) | 35 (5.9%) |
|  Adverse Event Not Related to Study Drug | 119 (40.6%) | 118 (39.7%) | 237 (40.2%) |
|  Adverse Event Categorized as Mild Related to Study Drug | 12 (4.1%) | 8 (2.7%) | 20 (3.4%) |
|  Adverse Event Categorized as Moderate Related to Study Drug | 15 (5.1%) | 5 (1.7%) | 20 (3.4%) |
|  Adverse Event Categorized as Severe Related lo Study Drug | 0 | 0 | 0 |
|  Adverse Event Categorized as Life Threatening Related to Study Drug | 0 | 0 | 0 |
|  Adverse Event Leading to Death Related to Study Drug | 0 | 0 | 0 |
|  Serious Adverse Event | 4 (1.4%) | 14 (4.7%) | 18 (3.1%) |
|  Serious Adverse Event Related to Study Drug | 0 | 0 | 0 |
|  Adverse Event Leading to Study Discontinuation | 2 (0.7%) | 3 (1.0%) | 5 (0.8%) |
|  Adverse Event Leading to Death | 1 (0.3%) | 3 (1.0%) | 4 (0.7%) |

---

Abbreviations: ASA = Amniotic Suspension Allograft; PM = Patient Months of Exposure.

Note: The safety population includes all randomized subjects who received 1 injection of ASA or placebo, but analyzed as randomized.

Subjects who reported more than one adverse event within each category were only counted once. A treatment emergent adverse event is defined as an adverse event with an onset or worsening at the time of or following the administration of the study drug. Adverse events with a missing relationship are considered as related.

Source: Listing 16.2.7.1

------

Organogenesis 19OA (First Phase 3 ReNu Study)

Table 14.2.1.1

Change from Baseline WOMAC Pain Scale at 6 Months - Control-based Mean Imputation

FAS Population

---

| | | |
|:---|:---|:---|
|  | ASA | Placebo |
| Statistics | (N *=* 258) | (N *=* 257) |
|  WOMAC Pain Scale |  |  |
|  Change from Baseline to Week 26 |  |  |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; n | 197 | 196 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Mean (SD) | -6.1 (4.71) | -5.9 (4.97) |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Median | -6.0 | -6.0 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Q1, Q3 | -9.0, -2.0 | -9.0, -2.0 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Min, Max | -18, 6 | -20, 6 |
|  Number of subjects with missing data | 61 (23.6%) | 61 (23.7%) |
|  CFB LS Mean Estimate | -6.0 | -5.3 |
|  Standard Error | 0.33 | 0.31 |
|  CFB LS Mean Difference (ASA - Placebo) | -0.7 |  |
|  One-sided 97.7% CI of CFB LS Mean Difference | [-Inf to -0.050] |  |
|  p-value | 0.0177 |  |

---

Abbreviations: CFB *=* change from baseline; CI = confidence interval; Inf = Infinity; KL *=* Kellgren-Lawrence; MMRM = Mixed-Effects Model Repeated Measures; WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index.

Baseline is defined as the last non-missing measurement preceding the single injection (ASA or placebo). Negative change from baseline indicates better health.

Subjects withdrawing early from the trial or using rescue medication and/or prohibited therapies, except the protocol permitted rescue analgesic medication prior to 6 months or who had knee replacement surgery on index knee prior to Month 6 will be considered with missing data at Week 26.

A control-based mean imputation (Mehrotra et al, 2017) is used to handle missing data. Mixed-Effects Model Repeated Measures is used in the steps of the imputation with the baseline WOMAC Pain Score value and KL grade as covariates. Estimation of the LS Mean is done at the observed overall means of the covariate based on subjects from the FAS population. Visits included in the MMRM are Week 1, Week 6, Week 12, Week 18, and Week 26 with visit included as a fixed factor and baseline-by-visit and treatment-by-visit as interaction terms. Unstructured covariance is used to model the intra-subject variability.

p-value is derived from a t-test 1-sided at alpha level 0.023.

Source: Listing 16.2.6.1.

------

Organogenesis 19OA (First Phase 3 ReNu Study)

Table 14.2.2.1

Change from Baseline WOMAC Function Scale at 6 Months - MMRM

FAS Population

---

| | | |
|:---|:---|:---|
| Statistics | ASA<br> (N=258) | Placebo<br> (N=257) |
|  WOMAC Function Scale |  |  |
|  Change from Baseline to Week 26 |  |  |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; n | 196 | 195 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Mean (SD) | -18.7 (15.62) | -19.1 (16.62) |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Median | -19.0 | -16.0 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Q1, Q3 | -28.0, -6.0 | -29.0, -8.0 |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Min, Max | -63, 17 | -67, 21 |
|  CFB LS Mean Estimate | -17.75 | -17.11 |
|  95% CI of CFB LS Mean | [-19.76 to -15.74] | [-19.12 to -15.10] |
|  CFB LS Mean Difference (ASA - Placebo) | -0.64 |  |
|  95% CI of CFB LS Mean Difference | [-3.45 to 2.17] |  |
|  p-value | <.0001 |  |

---

Abbreviations: CFB = Change from Baseline; CI = Confidence Interval; KL = Kellgren-Lawrence; LS = Least Squares; Max = Maximum; Min = Minimum; MMRM = Mixed-Effects Model Repeated Measures; SD = Standard Deviation; WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index.

Baseline is defined as the last non-missing measurement preceding the single injection (ASA or placebo). Negative change from baseline indicates better health.

Mixed-Effects Model Repeated Measures is used with WOMAC Functional scale score at baseline and KL Grade as covariates. Visits included in the MMRM are Week 1, Week 6, Week 12, Week 18, and Week 26 with visit included as a fixed factor and baseline-by-visit and treatment-by-visit as interaction terms. Unstructured covariance is used to model the intra-subject variability.

p-value is derived from the MMRM model at alpha level 0.05.

Source: Listing 16.2.6.1.

------

Organogenesis 19OA (First Phase 3 ReNu Study)

Table 14.3.1.1

Overall Summary of Treatment Emergent Adverse Events

Safety Population

---

| | | | |
|:---|:---|:---|:---|
| Subjects with at Least One Treatment Emergent: | ASA<br>(N *=* 255)<br>(PM *=* 2792.64) | Placebo<br>(N *=*259)<br>(PM *=* 2858.91) | Total<br>(N *=* 514)<br>(PM = 5651.55) |
|  Adverse Event | 139 (54.5%) | 136 (52.5%) | 275 (53.5%) |
|  Adverse Event Categorized as Mild | 82 (32.2%) | 78 (30.1%) | 160 (31.1%) |
|  Adverse Event Categorized as Moderate | 88 (34.5%) | 87 (33.6%) | 175 (34.0%) |
|  Adverse Event Categorized as Severe | 13 (5.1%) | 9 (3.5%) | 22 (4.3%) |
|  Adverse Event Categorized as Life Threatening | 0 | 2 (0.8%) | 2 (0.4%) |
|  Adverse Event Related to Study Drug | 16 (6.3%) | 7 (2.7%) | 23 (4.5%) |
|  Adverse Event Not Related to Study Drug | 131 (51.4%) | 136 (52.5%) | 267 (51.9%) |
|  Adverse Event Categorized as Mild Related to Study Drug | 9 (3.5%) | 3 (1.2%) | 12 (2.3%) |
|  Adverse Event Categorized as Moderate Related to Study Drug | 7 (2.7%) | 4 (1.5%) | 11 (2.1%) |
|  Adverse Event Categorized as Severe Related to Study Drug | 0 | 0 | 0 |
|  Adverse Event Categorized as Life Threatening Related to Study Drug | 0 | 0 | 0 |
|  Adverse Event Leading to Death Related to Study Drug | 0 | 0 | 0 |
|  Serious Adverse Event | 17 (6.7%) | 13 (5.0%) | 30 (5.8%) |
|  Serious Adverse Event Related to Study Drug | 0 | 0 | 0 |
|  Adverse Event Leading to Study Discontinuation | 3 (1.2%) | 7 (2.7%) | 10 (1.9%) |
|  Adverse Event Leading to Death | 0 | 3 (1.2%) | 3 (0.6%) |

---

Abbreviation: ASA = Amniotic Suspension Allograft; PM *=* patient months of exposure.

Note: Subjects who reported more than one adverse event within each category were only counted once. A treatment emergent adverse event is defined as an adverse event with an onset at the time of or following the administration of the study drug.

PM cumulative exposure calculated by adding individual exposure, defined as (date of end of study - date of injection) / 30.4375 for each subject.

Source: Listing 16.2.7.1.