Ladies and gentlemen, thank you for standing by and welcome to the MiMedx Fourth Quarter 2020 Operating and Financial Results Conference Call. At this time, all participant lines are in a listening mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star zero. I would now like to hand the conference over to your speaker today, Jack Howarth. Thank you. Please go ahead, sir.
Thank you, operator. Good morning, everyone. Welcome to the MiMedx fourth quarter and full year 2020 operating and financial results conference call. With me on today's call are Chief Executive Officer, Tim Wright, Chief Financial Officer, Pete Carlson, Executive Vice President and Chief Commercial Officer, Dr. Rohit Kashyap, and Executive Vice President of Research and Development, Dr. Robert Stein. Tim and Pete will provide operating and financial results for the fourth quarter and full year 2020. At the conclusion of their remarks, Tim, Pete, Dr. Kashyap, and Dr. Stein will be available for your questions. Before we begin, I would like to remind you that comments made during today's call include non-GAAP financial measures, and we provide a reconciliation to GAAP in our press release, which is available on our website at www.mimedx.com. Also, our comments today will include forward-looking statements.
Although the company believes that the expectations reflected in such forward-looking statements are based upon reasonable assumptions, actual outcomes and results are subject to risks and uncertainties and may differ materially from those anticipated due to many factors. Listeners are directed to the cautionary notes in the press release issued yesterday, as well as the risk factors set forth in MiMedx 2020 annual report on Form 10-K for factors that could cause actual outcomes and results to differ materially from those reflected in the forward-looking statements. The company assumes no obligation to update or supplement any forward-looking statements except as required by law. With that, I'm now pleased to turn the call over to Tim Wright. Tim?
Thank you, Jack. Good morning, everyone, and thank you for joining us. 2020 was a foundational year for MiMedx. We focused on a number of operational and financial initiatives in order to move the company forward in its transformation, propel its pipeline, and regain momentum. Before I get into 2021 strategic initiatives, let me review some of the many accomplishments from last year. First, let me talk about the efforts to restore the business and our accomplishments there. We recruited experienced, high-integrity leaders with subject matter expertise across the board. We've converted 90% of our executive and senior management during this period. We also did a fantastic job of reconstituting the board, focusing on improved governance, diversity, and expertise. We're also pleased to announce Dr. Phyllis Gardner is joining our Board. Dr. Gardner is regarded for her contributions and accomplishments across academia, biotechnology, and the healthcare industry.
Dr. Gardner is a Professor of Medicine at Stanford University School of Medicine and a distinguished business leader. She brings more than 35 years of experience to the company, marked by numerous national awards and honors. She has conducted extensive research in cell biology and gene therapy and is widely published in the fields of cell biology and pharmacology. Her insight, perspective, and strategic expertise, combined with our existing board, will be invaluable as we propel our late-stage pipeline towards biologic registration and guide MiMedx into the future of regenerative therapeutics. The efforts to restore our business start with getting current on our financial reporting. In addition, we raised needed capital, $150 million, through financing led by EW Healthcare. Also, an important aspect of restoring the business was relisting on Nasdaq on November fourth.
In addition to restoring the business capability and capacity with creating value in the business, long-term value for shareholders, we completed our Knee OA enrollment of our phase II-B study. We completed plantar fasciitis enrollment in a phase III study. We launched a new product out of our EPICORD franchise called EPICORD Expandable. This offers the potential to provide physicians and patients with expanded wound coverage economically. In addition, we received EPIFIX diabetic foot ulcer coverage from the largest U.S. commercial payer in the U.S. 2020 was a busy year. I'm proud of everything that we accomplished. Now we're in a position to begin really focusing on the operating aspects of our business and investing in it. We are the pioneers in using birth tissue as a platform for regenerative medicine. We believe our biologics pipeline and our advanced wound care business will create extraordinary value for our shareholders.
Our primary goal is twofold. Improve access and utilization of our wound care products, number one, and by doing so, we will grow our top line by over 10%. Number two, accelerate our novel late-stage pipeline in regenerative medicine. In addition to those two primary objectives, to support that, we have reorganized, reincentivized, and reinvested in our sales force in order to capture momentum and support for the growth of our core wound care business. We're confident also about completing the registration process for EPIFIX in Japan. We anticipate we receive registration approval mid-year 2021. This presents another attractive growth opportunity for MiMedx. These are very exciting times for our company. Let me get started by giving you an overview of two very impressive pipeline assets. First pipeline opportunity is plantar fasciitis.
As you know, our phase II-B study was completed and demonstrated a 76% reduction in pain versus control at three months. We've completed enrollment of our phase III study, which included 277 patients in September of 2020. Our last patient out is anticipated to be Q2 2021. Let me give you our estimates on BLA filing. We anticipate on filing our BLA in the first half of 2022. We also have plans to accelerate that, if at all possible, we will file in late fourth quarter. We anticipate FDA approval and product launch predicated on when we submit our application. The earliest would be fourth quarter of 2022 or later, the first half of 2023. The market for plantar fasciitis has been articulated before in some of our calls. Just as a reminder, approximately two million patients are treated annually for PF.
About 10% of those patients are recalcitrant and require advanced therapies like corticosteroids. We believe in the first year, the potential candidates for an injection of our AmnioFix product would be about 20,000-50,000 patients. It's important to note that recovery from chronic plantar fasciitis tends to be lengthy, and recurrence is very common in this patient setting. Our second pipeline opportunity is in knee osteoarthritis. You all know, this is a very significant unmet need. We completed our enrollment in our phase II-B trial in September as well. Let me remind you that that trial enrolled 447 patients, a large phase II-B trial. The last patient out for the six-month blinded observation will be late 2021. Included in this trial is also a six-month open label extension that allows patients the option to receive micronized dehydrated human amnion/chorion membrane or AmnioFix.
What's important to note from our two pipeline assets here is that there are several enabling factors that are afforded by filing our plantar fasciitis registration. One, we're advantaged by GMP readiness that's afforded here by filing the PF. This means that we don't have to go through that process again with the agency. As you know, the company was first to receive RMAT designation. This advantages the company in having frequent dialogue around clinical trial protocols, surrogate endpoints, et cetera. It also allows us the opportunity to discuss our manufacturing process and release criteria. The current timelines in the market is as follows. We'll be meeting with the FDA in mid 2021. We'll be reviewing our phase II-B trials, presenting our phase III protocol, and we plan to initiate our phase III trial in the first half of 2022, if not sooner.
We would anticipate a BLA filing in the second half of 2024 or the first half of 2025. FDA approval, we anticipate would be the second half of 2025 or the first half of 2026. Both pipeline opportunities we think offer this company exciting potential to create value for our shareholders, more importantly, value for patients who are suffering from these particular issues. As we know, the Knee OA market is very large. It's growing at around 2% a year off of a base of 17.5 million patients. Today, about 4.4 million patients are being treated with intra-articular injections, and there are about 8.8 million injections per year. When you do the math around this and you look at what we think based on our labeling, how we penetrate this market, we think annually, we would treat 1 million-1.5 million patients.
That would be on an annual basis. If the efficacy is proven in our phase III trial, this would be a very important new tool for physicians to treat knee osteoarthritis. Shifting to our commercial organization, as I mentioned earlier, we have redesigned the organization, reincentivized them to focus on distinct areas of promotion with our products that are used for DFUs and VLUs. We have a very robust commercial infrastructure that is supported by our expanding medical science liaison program, clinical evidence, and improved reimbursement. Today, we cover over 300 million lives. Contractually to support our efforts to pull through and provide access to our products, we currently have multi-year contracts in place with the largest GPOs and IDNs. Our field-based reimbursement and national account teams are also used to accelerate the commercial adoption of our products.
I've covered off our strategic initiatives, which can be summarized as focused on our pipeline, focused on our core business. I'm going to turn the call over to Pete Carlson.
Thank you, Tim, and good morning, everyone. Today, I will discuss our fourth quarter and full year 2020 results and comment on some of the underlying trends we are seeing in the business. I do want to take a moment and reiterate some of the achievements MiMedx accomplished in 2020. As a company, the reason we are working to restore our financial reputation is to support the continued delivery of products that make a difference in the lives of patients and their families. Many of us have seen the impact that our PURION engineered technology can have as an advanced treatment option for hard-to-heal acute and chronic wounds. Our 700+ employees are dedicated to delivering the level of quality and excellence our customers deserve, and I appreciate the team's commitment to elevating the standard of patient care.
In 2021, as we have talked about, we are increasing our investments in both parts of our business, our core advanced wound care portfolio, and our late-stage pipeline. All amniotic tissue products are not the same, we believe our differentiated platform is positioned to exceed market growth. Recent efforts in our commercial organization position us for this growth in the coming year. We are 265 sales personnel strong and plan to increase that number in 2021 by 10% or more, along with aligning territories to ensure we have the right people in the right places. The team is leveraging recent coverage by the largest U.S. commercial payer for EPIFIX, our flagship brand, as a proven and medically necessary treatment option for diabetic foot ulcers. We are also increasing our medical education efforts and personnel to help pull this through with our customers.
Returning to 2020 results, I would note that the impact of the company's transition and revenue recognition methodology on quarterly results is now behind us. I do want to clarify the impact on our reported full-year results. Net sales for the full year ended December 31st, 2020, were $248 million, primarily recognized on an as-shipped basis, compared to $299.3 million for 2019, primarily recognized on a cash received basis. Net sales for 2020 and 2019 include the benefit of $7.8 million and $29.6 million, respectively, resulting from the change in revenue recognition methodology. Adjusted net sales, which exclude impacts of the company's transition and revenue recognition, were $240.5 million in 2020, a decrease of 11% from 2019. This decrease primarily reflects access restrictions, decreases in elective procedures, and cost-saving measures implemented by hospitals as a result of the COVID-19 pandemic.
In looking at a breakdown of our tissue and umbilical cord products, the skin substitute part of our advanced wound care business, the decline is much less in 2020 compared to 2019. This can also be seen in our quarterly trends. Reported adjusted net sales for the fourth quarter are flat compared to the same period in 2019. Excluding the impact of out-of-period accruals in the fourth quarter of 2020, adjusted net sales are down slightly, while our tissue and umbilical cord products are up slightly in that period. Gross margin in the fourth quarter of 2020 was 84.2%, compared to 83.4% in the fourth quarter of 2019, reflecting improved manufacturing efficiencies and lower levels of scrap.
For the full year of 2020, we saw a slight gross margin decline from 85.6% in 2019 to 84.2% in 2020, primarily a result of the higher quality standards of Current Good Manufacturing Practices we have been implementing since the second half of 2019. Selling, general, and administrative expenses, or SG&A, for the fourth quarter of 2020 were $48.7 million, or an increase of 7.2% compared to the fourth quarter of 2019. Spending on corporate initiatives and non-executive stock-based compensation contributed to this increase for the quarter. For the full year, we saw a decrease in SG&A, driven in part by the company's efforts to manage expenses in response to the COVID-19 pandemic. As previously disclosed, we implemented a number of initiatives, including a temporary salary reduction and travel restrictions. In addition, reduced commissions resulting from a reduction in sales contributed to the full-year decrease.
Research and development expenses were $3.4 million for the fourth quarter of 2020, compared to $2.7 million for the fourth quarter of 2019. For the full year, our research and development expenses were $11.7 million in 2020 compared to $11.1 million in the prior year. Consulting fees related to the company's clinical research efforts drove this increase. The company expects these costs to increase as much as threefold in the coming year. As previously mentioned, this investment supports our future growth objectives that Tim outlined, although the amount could vary depending on the results of our clinical study readouts in the second quarter of this year. We plan to continue working towards the filing of our biologic license applications, file new or additional investigational new drugs in the first half of the year, and publish further clinical and scientific research, including efficacy and economic data.
Investigation, restatement, and related expenses for the fourth quarter of 2020 were $20.4 million, consisting of costs incurred under indemnification agreements with the company's former management and directors and costs related to certain legal matters involving the company, including resolution of some matters as I have previously indicated. In the year-ago period, these totaled $20.1 million and consisted of legal and restatement expenses. For the full year 2020, investigation, restatement, and related expenses were $59.5 million compared to $66.5 million in 2019. In 2021, the company expects a significant decline in investigation, restatement, and related expenses prior to any resolution of the pending securities class action matter. Of course, actual results may vary and depend in part on the outcome of certain legal matters we disclose in Note 14 of our 2020 Form 10-K.
I remind you that the audit committee investigation was completed in mid-2019, and the restatement was completed in mid-2020. We do not expect to incur those related expenses going forward. Further, we are not currently incurring advancement and indemnification expenses for the former CEO and COO because judgments of conviction have been entered against these individuals, and it is the company's position that the judgments, as they now stand, cut off our advancement and indemnification obligations. Turning to the bottom line, net loss in the fourth quarter of 2020 was $16.6 million, compared to a net loss of $7.5 million in the fourth quarter of 2019. Net loss for the full year 2020 was $49.3 million and includes an $8.2 million loss on extinguishment of debt of the company's previous term loan, as well as a $6.7 million benefit from the change in revenue recognition.
Net loss for the prior year was $25.6 million, including a $24.5 million benefit from the change in revenue recognition. Adjusted EBITDA was $10.3 million in the fourth quarter of 2020 compared to $14.1 million in the fourth quarter of 2019. The full year adjusted EBITDA was $30.6 million or 12.7% of adjusted net sales, compared to $42.1 million or 15.6% of adjusted net sales in the prior year period, reflecting the factors I have already discussed. Now let me review our cash position. As of December 31st, 2020, the company had $95.8 million of cash and cash equivalents, compared to $69.1 million as of December 31st, 2019. Our healthy cash position gives us the financial flexibility to invest in initiatives that strengthen our core business and invest in research and development activities, as I outlined earlier.
Turning to 2021, we expect our adjusted net sales will increase 10% or more over the prior year, assuming we are able to sell our micronized, particulate, and umbilical cord products for the full year. Again, actual results may differ materially, and there are some caveats as we have indicated. Specific to our micronized and particulate products, as an example, if these products are required to be removed from the market following the period of enforcement discretion, we estimate the negative impact on our expected 2021 net sales could be in the range of $20 million-$25 million. As Tim mentioned, our dialogue with the FDA continues, and we expect to gain additional clarity on the full impact and timing of enforcement discretion in the coming months.
You will note that we have included our umbilical cord products within those that could potentially be impacted by the end of the period of enforcement discretion. This disclosure is primarily based on a limited number of communications from the FDA to other companies selling umbilical cord products, some of which are marketing their products outside of the diabetic foot ulcer and venous leg ulcer areas where our products are currently utilized. The reasoning and analysis here is different than the micronized and particulate products, which are viewed as more than minimally manipulated. The discussion for the cord products focuses on the homologous use standard and the way these products are described and marketed. We are working to gain additional clarification of the potential impact within the FDA guidance and will keep you updated.
Throughout recent presentations, we have outlined key drivers to achieve growth in our core business, including enhancing the value of our portfolio, expanding the market through awareness and data, targeting new business with product innovation, and pursuing international expansion. While we are optimistic about our 2021 growth potential, I remind you that we still are in the midst of the pandemic, and in certain areas, local or regional surges of COVID-19 have continued. We do know that chronic non-healing wounds are not getting better without treatment, and our commercial team is positioned to address the needs of this patient population. In closing, as you expect, we are continuing our other outreach efforts and dialogue with investors and analysts. Another benefit of our NASDAQ listing is the increased opportunity to participate in industry conferences, and we have enjoyed the chance to continue sharing our story with members of the financial community.
I will now turn the call back to Tim.
Thank you, Pete. Looking forward, our focus for the company is on our growth drivers for 2021. They're broken down in R&D, operations, and commercial. Let me just quickly review those. We plan the second half of the year to do an interim data readout, accelerate our late-stage pipeline. For example, accelerate the filing of our PF application into the fourth quarter. On Knee OA, accelerate our phase III clinical trial into the first half of the year. We have an ongoing effort through our medical affairs organization and R&D to continue to publish peer-review articles that are clinically oriented, scientifically oriented, and have a position on economics. Additionally, we plan to file new INDs in 2021 as well to continue to support the company to achieve its goal of advancing scientific rigor of this category in a way that makes a significant difference for patients.
Moving from R&D to operations, we plan to validate our manufacturing facilities to a Current Good Manufacturing Practice standard. In addition, we'll continue our high rate of fulfillment above 95%. Commercially speaking, we plan to grow our top line by 10%, our sales force by 10% as well, augmented by our efforts in medical affairs. We are hopeful that we will receive Japanese approval mid-year and reimbursement approval for our products by year-end. Additionally, we'll continue to evaluate organic growth opportunities inside our R&D and product development organizations. Finally, as you can see from Pete's presentation and mine, we're investing in the core business for expanded growth. In addition, we have a laser-like focus on accelerating our pipeline. I'd like to thank you for listening today. Operator, you can now open up the lines for questions. Thank you.
Thank you. As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from Sean King with H.C. Wainwright. Your line is now open.
Hi. Thank you for taking my question. My first question is, how confident are you that FDA might allow you to continue marketing your micronized product for the full year 2021?
Hey, Sean, that's a great question. This is Tim. It's hard to anticipate exactly where the FDA is going to fall down on that. I don't have a crystal ball. However, over the last 18 months, we've had communication with them about everything that we're doing in our manufacturing facility to convert that to GMP, as well as continue to conduct clinical trials, as well as file new INDs. I think this is perfectly in line with what the agency is asking the industry to do.
I see. How much pandemic impact do you expect for 2021, obviously things are hopefully getting better with the vaccination program? What is your plan to mitigate potential risk?
Sean, it's Pete Carlson. We haven't given any specifics one way or the other about the first quarter relative to expectations or what's any numerics about what's going on. As I mentioned in my remarks, there does continue to be some local and regional impact, and I'd use the term mixed again. It's not very technical, that's what we talked about earlier in the year or a year ago. It, I think, is more isolated than certainly what we saw 10 months ago, 12 months ago. The other thing, there was a little bit of lost time from weather. Everybody knows that there was that freak storm in Texas. Texas is a high populous state and has a high incidence of diabetes. Otherwise, we haven't given any specifics.
Okay. That's good. One last quick one. I apologize if I missed this during the call earlier, is there any data readouts from the pipeline product for this year? Maybe I missed that.
It's Pete again. I'll just give you some calendar and Dr. Stein can fill in. Yes, there are readouts coming in the first half of the year on really all three of the trials we have going on in the musculoskeletal area. Dr. Stein?
Yes, Pete. Hi. As Pete said, we will be completing the last patient out of our phase III for plantar fasciitis and Achilles tendinopathy in the first half of the year, and we'll be processing and analyzing the data probably for about a quarter. We'll then want to meet with the FDA. At the appropriate time, we'll be able to describe those results. We're very much looking forward to the outcomes. The Knee OA trial, the last patient will have completed the six-month blinded observation period at the same time as the other two phase III complete. That's in the phase II. We'll still have a six-month open label extension that the FDA requires. We'll be moving that program forward as rapidly as we can. You may remember we have RMAT designation for that product. We will be discussing the results with the FDA.
We'll time our public description of the results so that they don't interfere with our opportunity to progress the product successfully through the regulatory path and towards registration. In all cases, we'll share the data as soon as it's prudent to do so with regard to regulatory interactions.
Okay. Thank you. That's very helpful. Thank you.
Sure.
Thank you. Our next question comes from John Vandermosten with SCR Zacks. Your line is now open.
Good morning, everyone. It sounds like the FDA has only had limited communication on enforcement discretion. I wanted to see how you think conversations might go with them. Would you reach out to them as we get closer to that end of May time period, or will they reach out to the industry, or will they do some kind of public announcement on how they're going to address this? Obviously, it will be company specific, or maybe not obviously, but it could be company specific given that some companies are doing studies and some aren't, and there's different positions out there. Can you look at it from that perspective for me?
Yeah, this is Tim. We've had fairly frequent dialogue with the agency over the last 18 months. Dr. Stein can opine on this as well. I believe that the agency's being very thoughtful about how they address this particular issue. As you've stated in your comments, some companies are not conducting any trials, while there are a limited number of companies that are actively engaged in filing INDs and conducting clinical trials, which would be more in line with what the agency provided in their 2017 guidance letter. I feel confident we've done everything that we can do to support the agency in their efforts to implement their guidance from 2017. Bob, do you have any additional comments?
I think that Tim summarized it very well. We support the FDA in their interest in trying to get better regulatory oversight for the products that are derived from tissues that are more than minimally manipulated and/or being used for something other than what they did in the donor. Excuse me for a second. We've worked hard to get our agents that are covered under the 351 regulations appropriately moved into clinical trials after filing INDs, or in some upcoming cases, IDEs.
We do believe that we'll be able to demonstrate that our products are safe and effective when used as directed in the indications we can specify, and we believe that we'll be making a successful transition to making them under cGMP, which are the conditions that the FDA is looking for. We are engaged in some constructive dialogues with the FDA, either through the RMAT interaction that we've fortunately got the designation for the Knee OA product of Regenerative Medicine Advanced Therapy, or through other interactions that the company is pursuing with the agency.
Okay.
Thank you, Bob.
Oh, I'm sorry. Go ahead.
I was just thanking Bob. Go ahead, please.
Just another question on that same topic. What happens to product in the channel if enforcement discretion is ended? I guess you may anticipate that and pull back, or will it be able to be used, or how do you anticipate that going forward?
The FDA has not provided any perspective on that to us. Clearly, there's a strong track record in our own pharmacovigilance database around safety. If you think about what the FDA's central role is to the safety of the American public. I would be speculating to say that if enforcement discretion expires, I would be really speculating one way or the other way the FDA would view that. Obviously, we've looked at different scenarios with respect to your question, I think we're prepared either way how that rolls.
Okay. Great. As was mentioned, one of the facilities is cGMP compliant, and the other is almost there. What remains to be done at, I think it's the Marietta facility? What remains to be done to get that up to the cGMP standard as well?
John, it's Pete. Let me comment. Tim may want to add. What you're seeing there is just the response from the FDA. We have approached the remediation efforts at both facilities at the same time. We have submitted really in the middle of 2020 our what we felt like was a completed response to the findings. The FDA, frankly, has just chosen to respond to, report out on the facilities one at a time. From our side, nothing else to be done relative to response to that.
Tim, anything?
I think he covered it off well. For the first half of 2020, we made a significant effort to address any deficiencies that were noted in the December 19 audit. I think the agency's pleased with our response so far.
Okay. A big part of the growth plans include the health plans of commercial payers and getting them on board, and you've already put the largest commercial payer on, included them with MiMedx. What additional efforts are you making to add on others in this category? Obviously, having the largest payer is a pretty big feather in your cap, and are you able to leverage that to continue the trend to penetrate these targets?
John, it's Pete again. Let me start. With the addition of that largest commercial payer, we really have some indication coverage with all the commercial payers and obviously with the Medicare Medicaid system. It is now more about getting additional indications inside those payers' perspective, and that's clinical evidence. I'll let Tim and/or Bob comment on that.
I think that Bob can comment certainly on the clinical evidence, the peer-reviewed evidence that we're generating, as well as the work that we've done on a retrospective basis to look at the health economic impact of our products. Bob, do you want to comment on that more?
Yeah. I believe that we have an interesting circumstance in that we've distributed over 2 million of our various products to patients for use since their introduction, and we have an excessively clean safety track record for those products. We've been able to do some very interesting retrospective work in the Medicare database to demonstrate the utility of the sheet products in diabetic foot ulcer, and some work in conjunction with analysis about how they would function in the United Kingdom in terms of the cost for additional quality of life years, all of which demonstrate quite nicely the value of the interventions. We've also been ahead of the curve in conducting randomized controlled trials of our sheet products in diabetic foot ulcer and venous leg ulcer, including comparisons to some of the competitor products, and shown superior performance.
We are continuing to gather data on the sheet products in the real world and how they perform. In addition, we have the 351 products, the micronized amnion chorion membrane, that are in advanced clinical trials and have already been in many thousands of patients, probably more than 100,000 patients. The number there is a little bit more difficult to determine. They have an exceptional safety record and lots of evidence for their utility in settings such as plantar fasciitis and knee osteoarthritis. Earlier studies have formed the basis for the current later stage programs that we've described in the call.
Okay. Yeah, it sounds like you've got a lot of ammunition for your sales team to use to go out there and get further penetration. You're also adding 10% in sales reps, I think was that maybe 26 to 30 people, over the next year. When you talk about 10% growth, overall top line, I guess, does that just include these new sales reps that you're adding on? Is there some kind of individual sales rep growth in there as well? How will that all come together over the next year?
Rohit, would you like to address the question?
Yes. Thanks, Tim. Yeah, in terms of the growth, I think there are multiple factors driving it. Growth is a factor of sales force effectiveness. Obviously, as we add and increase our sales team scale, people will come on board. It will typically take anywhere between six and 12 months for the salespeople who come on board to be fully effective. The sales growth is a combination of both your existing sales team growing with the market or above the market with the clinical evidence and data that we just talked about utilizing it with the support of getting more people informed and aware of the different options that are available to them for treatment, as well as the addition of the new head count. There are multiple factors that lead up to achieving above market and above 10% growth.
Okay. That's very helpful. Then jumping to the KOA indication and the grant of RMAT designation. It seems like what you're providing now in your estimates is a very conservative approach that doesn't really take advantage of that RMAT designation and some of the benefits it confers, such as expedited treatment of that. Can you talk about perhaps some benefits that are possible for that to perhaps get it approved with maybe data that you've already generated or perhaps an extension on studies that you've done? I just want to hear some hypothetical opportunities that might be available to a company with what you have on your plate right now.
As you know, there are probably less than 50 products that have received RMAT designation. The prior management team here was very successful in achieving RMAT status. I think it's probably the first biologic like this to do that. All said, you're absolutely correct. It does afford you the luxury of more frequent dialogue with senior management at the FDA. We're taking advantage of that for sure. The two areas I think are very important to have dialogue with the agency on, number one is your clinical trials. As you know, we're preparing a protocol for our phase III trial, Knee Osteoarthritis. We will definitely exercise our RMAT status to be aligned with the FDA on the phase III trial. I think it's particularly important that Dr. Stein can articulate more.
We conducted a very large phase II-B trial, and if we replicate the results in that phase II-B trial to the ones that Dr. Alden in his retrospective trial conducted, I think we'd be in good shape there. The currency for the agency is data, and I think that's what our team is focused on, is working with the agency around creating the best data we can. That data is not only clinical data, but also data that we produce in our manufacturing area, all the chemistry, manufacturing, and controls. That's another area of dialogue that's very important with the agency. RMAT doesn't subordinate the FDA's standard around product approvals. It just is enabling you to have more frequent dialogue so you can streamline your decision-making process around manufacturing release, and clinical trials. Bob, would you like to add to that, please?
I think you said it very well. I think that the RMAT designation is an indication that the FDA believes you have a potentially important medicine and indicates that they are interested in a somewhat more collaborative way of progressing the product through the regulatory process. We're very glad to have that. It's not an easy designation to get, and I think it is based on the exciting data that were presented up until the point where the discussion was held with the FDA.
Okay, great. Last question from me is just on the new INDs that you're going to be filing this year. I think they're in advanced wound care. Can you go into a little bit more detail there on what you'll be pursuing and some of the exciting indications that you may be able to solve if these are successful?
Bob?
I'd be happy to give you a little bit of information about that. We have both the micronized injectable material for outpatient use, where it's often used in patients with chronic non-healing wounds. Sometimes you can't have the sheet products be fully effective, either for compliance or other reasons. We're interested in looking at injecting the micronized material around the edges of diabetic foot ulcer and helping to recruit stem cells and drive the healing process there. There's also interest in the surgical use of the micronized material. It's often being employed to help surgical incisions heal, and we're going to be filing an IND to support that application.
Many patients who are either obese or diabetic or older or malnourished or smokers are known to have a lower likelihood of having successful healing after surgical incisions. There's use in that setting, and we're going to be exploring that. The material that is a larger particle size, called AmnioFill, is often used to fill soft tissue defects in the operating room, either in things like amputations or traumatic wounds or pilonidal cysts or other settings where you have a missing tissue and you want to put in something that provides extracellular matrix and growth factors, and that's what AmnioFill does. We'll be exploring that under an investigational application as well.
Great. Thank you, guys.
Thanks, John.
Thank you.
Take care, John.
As a reminder, to ask a question, you will need to press star one on your telephone. Our next question comes from Eiad Asbahi with Prescience Point. Your line is now open.
Thanks for taking my question, guys. This question is for Tim and Bob. Just from backing up and looking at the pipeline from a modeling standpoint, it sounds like you guys are saying that AmnioFix has the potential to capture one to 1.5 million patients with Knee OA, which seems to make sense in light of its competitive positioning in terms of its safety profile and benefits relative to those of alternative treatments such as NSAID, corticosteroids, and HA. I've heard you guys talk in some of the previous conferences about Knee OA potentially more likely than not taking place in both knees of each patient. How many shots per patient should we be thinking about in terms of modeling this out? Are we thinking three shots per patient per year or four shots per patient per year?
Can you guys elaborate on how you're thinking about that?
This is Tim, Eiad. I'll let Bob talk about it from his viewpoint. To answer your question directly, as a patient progresses, the idea of them having another injection is certainly realistic. It's just when they decide to treat the other knee, if you will. The idea of bilateral treatment is dialed into our calculus. The 1 to 1.5 patients treated, that's one injection per patient. That was the initial assumption. As we do more primary research, we talk to our advisory board and key opinion leaders, we're starting to change our perspective on that. A patient throughout the year for a 12-month period could receive between one and four injections. It'd be very patient dependent, depending on where they are in the life cycle of their degenerative disease.
I think we do know that there's a high probability that once you have Knee OA in one knee, you will eventually get it in your other knee. It depends on how the physician wants to begin to treat that patient. Bob?
Yeah, I think Tim made some good points. Eiad, you're absolutely right that many patients end up with bilateral Knee Osteoarthritis. Once you have one bad knee, you start to take the weight off that, and you put more weight on the other knee, and that makes the other knee degenerate more rapidly. It's not uncommon that the two knees may not become as affected at the same time, but it's pretty often the case that both knees become affected. I think it's reasonable to believe that many patients will be getting bilateral injections. In our current phase II study, we're exploring the duration of the effect after one injection, and we are going to be administering some patients a second injection. We'll have a better sense of that.
I don't think it's unreasonable to believe that the frequency of injection might be twice a year. Could actually be three times a year, but it probably looks like twice right now, and we're continuing to evaluate that. I think that the exciting aspect of the product is that it may delay the need for expensive knee replacements. In the anecdotal experience of Dr. Alden, who did the earlier work that led to our phase II trial, many patients who were scheduled for knee replacements actually not only didn't return for knee replacements but came back and asked for having medicine injected into some of their other achy joints. I think it is not unreasonable to speculate that we'll be using multiple injections per year.
Bob, I think it's important for our audience that could you just drill down a little bit more thinking around adding the option for the patient to receive an injection even though they were on placebo?
The initial design for the phase II study just had a single injection followed either by the active drug, micronized human amniotic allograft or by placebo. The patients were followed blindly for six months. There was a six-month open-label extension just for safety. What we did was we modified the design and let the FDA know that we had done so that patients in the second six-month interval, if they felt like they didn't have adequate pain control, could receive an injection of the active material. From that design, we'll see what happens with how long the first injection provides relief, whether the second injection restores relief in patients for whom the relief has faded.
We'll have an interesting setting where we'll have people who were on placebo during the first six months who then receive active drug, and we can have a very clear sense of whether the material is providing them relief as well. We like that design a lot, and I think we'll learn a lot by how it provides us that information.
Thanks, Bob.
Sure.
Thank you for that. I kind of want to just translate what this all means. The numbers, when you think about them, are quite staggering. I want to ask you guys, Tim and Bob, if this is conceivable, but at 1 million to 1.5 million patients, three injections per year, and a price per shot of $1,500-$2,000, you get a revenue range, a peak sales range of $4.5 billion-$9 billion. Is that conceivable?
Eiad, certainly when you do the math. That's why you have some of the largest pharmaceutical companies doing research in Knee OA. It's a complicated area. Yeah, if you can do the math on one injection per year, two injections a year times the patients. When you look at other therapies, the viscosupplementation therapies, there is a regimen that's established and something that rheumatologists and surgeons are accustomed to. Patients in those settings with those particular type of treatment modalities may be getting on average two to three injections a year. We have to really understand this from coming out of our phase II-B trial and our phase III trial, what is going to be in the labeling for our drug.
It's very exciting for our R&D team and for our key opinion leaders to work with us in designing the protocol for phase III and also doing the analysis of phase II-B. We're going to have a lot more information about that. Your notion that when you do the math on it, we can't argue with you on the math. It's just that we know there's work to do ahead to prove this in the clinic. Bob, I don't know if you want to add any more to that.
[audio distortion], I'd like to just.
Go ahead, Bob
I do think it has very great potential as a medicine, and to have your knees replaced is not trivial. I had both mine replaced about five years ago. I would have loved to have had this medicine as an alternative. It's about $75,000 a knee to get them replaced. There's quite a bit of potential savings to the system to have an intervention that delays or perhaps even avoids the need for replacement. We have so far very promising results with this intervention, and it's not surprising because the micronized contains a large number of active growth factors and anti-inflammatory compounds that are perhaps the basis for some of what we're seeing with its efficacy.
Yeah, Bob, I think it's really important Eiad laid out a range there. We certainly think that this is a big range of opportunity here for us. I also think that as we did the analysis around the tissue engineering that the company had conducted or put in place as a pioneer in this area the scientists here early on developed a manufacturing process that preserved the inherent qualities of amniotic tissue membrane and also went to the extent of terminally sterilizing this product to make it a safe product. The whole supply chain here was well thought through way before the new management team arrived here. I think it's fair to say that will be an important consideration in the overall thinking and approval process.
Certainly, your clinical data will be important, but also how you make the product and how you make it the same way every time is going to be absolutely critical. We do have a strong team led by Scott Turner and Mark Rogers focused on our chemistry and manufacturing controls. Eiad, you're absolutely correct. There's a big range here. As we move through and get final labeling, we'll be able to tighten that up.
Thank you for that, Tim. Sorry, go ahead, Bob.
I was just going to say that Tim made an important point. The placenta is a remarkable organ. It has a plethora of growth factors that have been selected to work well in conjunction with each other over maybe 600 million years of evolution of placental mammals. You have fantastic starting material. What MiMedx has been particularly good at is converting that into a medical product that is stable and safe and contains the active growth factors in their native formats and is terminally sterilized so that the risk of transmitting any kind of infection is made minuscule. That's also going to make it a lot easier for us to make the transition to cGMP manufacture and producing a well-characterized, stable, and consistent product, which is going to be another key aspect of getting this product registered.
As Tim pointed out, we have a very good team working on that very hard in conjunction with the ongoing clinical studies.
Bob, thank you for that. I also think it bears mentioning that the revenue range that I just estimated seems to be extremely conservative when you think about it. Bob, you made an important point. If the product delays or prevents the need for a knee replacement, and our research indicates that is the case, but if it is true, then the pricing per injection could conceivably fetch $5,000 per injection if you're able to save the insurance companies the cost of funding knee replacements. Tim, isn't it true that that one to 1.5 million of patients you could potentially capture is in the U.S.A. alone?
That is true. That's our estimate range for the U.S. only.
Clearly, this is a global issue.
Right.
The company, given its size, we haven't had the capacity to examine that. You would think that that's certainly the right time for us to examine that.
Right
Our products we have approvals in the U.K. and Germany for our allografts, our skin substitutes. We're seeking approval in Japan for our skin substitutes there. We do think there's potential outside the United States that would somewhat mimic the opportunity in the U.S.
Okay.
I think it's also worth noting that there are probably north of 17 million people with moderate to severe osteoarthritis in the U.S. Many of those have bilateral disease, and the idea that there's fewer than 10% of those that would be suitable for treatment is an estimate based on the current injected products like hyaluronic acid, which frankly is only marginally helpful at best, or steroids, which there's a lot of concern about their use from the standpoint of long-term effects on joint deterioration. It may be that if this product performs as we hope it will, it will be suitable for use in a larger swath of that patient population, but that's speculation.
Thank you. This is my final question. As you're probably aware, clinical-stage biotech companies with potential blockbuster treatments in their pipeline can and have fetched massive multibillion-dollar-
Right
takeout offers following the publishing of phase I or phase II results. For example, just last year, Immunomedics was sold for $21 billion following the publishing of its phase II-B results, while Forty Seven was sold for almost $5 billion following the publishing of its phase I results. Given our belief that AmnioFix's peak sales could potentially exceed $8 billion, $12 billion, whatever, we believe that MiMedx could fetch a multibillion-dollar takeout offer following the publishing of its phase II-B KOA trial results. We believe it would be in the best interest of shareholders for the company to explore a potential sale to a strategic buyer after its phase II results are published. Is this something that management intends to take under consideration?
Eiad, we're considering every strategic option. Right now, we're focused on executing in our clinical trials, regaining momentum in our current core business, as well as making sure that our facilities are validated to GMP. There's work to do, and your theoretical notion here, certainly, there are a lot of examples of this in the industry. Right now, I think it's most important for us to execute against what we have on our plate for 2021, which includes the readouts for our trials. We have to get the securities behind us, and I must say that our board is keenly aware of these types of options.
Thank you, guys.
Yep. Thank you.
Thank you, Eiad.
Look, we're running up against other calls that we're going to have to make. 2020 was a very foundational year for us. 2021's going to prove to be transformational for MiMedx. I appreciate everybody's interest in this and look forward to talking to you throughout the day and next week. Thank you.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.